Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2000 Jun;108(Suppl 3):463–473. doi: 10.1289/ehp.00108s3463

Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure.

S D Holladay 1, R J Smialowicz 1
PMCID: PMC1637831  PMID: 10852846

Abstract

Fetal and early postnatal life represent critical periods in vertebrate immune system development. Disruption of such development by perinatal immunotoxic chemical exposure has been widely described in experimental animal models. The resultant inhibited postnatal immune responses in such animals are often more dramatic and persistent than those after exposure during adult life. Further, recent reports suggest that prenatal exposure to immunotoxicants may exacerbate postnatal aberrant immune responses (e.g., hypersensitivity disorders and autoimmune disease) in genetically predisposed rodents. Limited information is available regarding the possibility of inhibited postnatal immune capacity in humans as a result of developmental immunotoxicant exposure. The multifactorial nature of hypersensitivity and autoimmune responses will further complicate the elucidation of possible relationships between chemical exposure during ontogeny of the human immune system and immune-mediated disease later in life. Taken together, however, the available animal data suggest the potential for altered postnatal immune function in humans exposed to immunotoxicants (e.g., environmental chemicals and therapeutic agents) during fetal and/or early postnatal life.

Full text

PDF
463

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aboussaouira T., Marie C., Brugal G., Idelman S. Inhibitory effect of 17 beta-estradiol on thymocyte proliferation and metabolic activity in young rats. Thymus. 1991 May;17(3):167–180. [PubMed] [Google Scholar]
  2. Adinolfi M. Ontogeny of human natural and acquired immunity. Curr Top Microbiol Immunol. 1997;222:67–102. doi: 10.1007/978-3-642-60614-4_4. [DOI] [PubMed] [Google Scholar]
  3. Adkins B., Mueller C., Okada C. Y., Reichert R. A., Weissman I. L., Spangrude G. J. Early events in T-cell maturation. Annu Rev Immunol. 1987;5:325–365. doi: 10.1146/annurev.iy.05.040187.001545. [DOI] [PubMed] [Google Scholar]
  4. Alt F. W., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Andersson L., Nikolaidis E., Brunström B., Bergman A., Dencker L. Effects of polychlorinated biphenyls with Ah receptor affinity on lymphoid development in the thymus and the bursa of Fabricius of chick embryos in ovo and in mouse thymus anlagen in vitro. Toxicol Appl Pharmacol. 1991 Jan;107(1):183–188. doi: 10.1016/0041-008x(91)90342-c. [DOI] [PubMed] [Google Scholar]
  6. Andersson U., Bird A. G., Britton B. S., Palacios R. Humoral and cellular immunity in humans studied at the cell level from birth to two years of age. Immunol Rev. 1981;57:1–38. doi: 10.1111/j.1600-065x.1981.tb00440.x. [DOI] [PubMed] [Google Scholar]
  7. Baird D. D., Wilcox A. J., Herbst A. L. Self-reported allergy, infection, and autoimmune diseases among men and women exposed in utero to diethylstilbestrol. J Clin Epidemiol. 1996 Feb;49(2):263–266. doi: 10.1016/0895-4356(95)00521-8. [DOI] [PubMed] [Google Scholar]
  8. Barnett J. B., Barfield L., Walls R., Joyner R., Owens R., Soderberg L. S. The effect of in utero exposure to hexachlorobenzene on the developing immune response of BALB/c mice. Toxicol Lett. 1987 Dec;39(2-3):263–274. doi: 10.1016/0378-4274(87)90242-6. [DOI] [PubMed] [Google Scholar]
  9. Barnett J. B., Soderberg L. S., Menna J. H. The effect of prenatal chlordane exposure on the delayed hypersensitivity response of BALB/c mice. Toxicol Lett. 1985 May;25(2):173–183. doi: 10.1016/0378-4274(85)90079-7. [DOI] [PubMed] [Google Scholar]
  10. Barnett J. B., Spyker-Cranmer J. M., Avery D. L., Hoberman A. M. Immunocompetence over the lifespan of mice exposed in utero to carbofuran or diazinon: I. Changes in serum immunoglobulin concentrations. J Environ Pathol Toxicol. 1980 Nov;4(5-6):53–63. [PubMed] [Google Scholar]
  11. Beach R. S., Gershwin M. E., Hurley L. S. Altered thymic structure and mitogen responsiveness in postnatally zinc-deprived mice. Dev Comp Immunol. 1979 Fall;3(4):725–738. doi: 10.1016/s0145-305x(79)80065-8. [DOI] [PubMed] [Google Scholar]
  12. Beach R. S., Gershwin M. E., Hurley L. S. Growth and development in postnatally zinc-deprived mice. J Nutr. 1980 Feb;110(2):201–211. doi: 10.1093/jn/110.2.201. [DOI] [PubMed] [Google Scholar]
  13. Beach R. S., Gershwin M. E., Makishima R. K., Hurley L. S. Impaired immunologic ontogeny in postnatal zinc deprivation. J Nutr. 1980 Apr;110(4):805–815. doi: 10.1093/jn/110.4.805. [DOI] [PubMed] [Google Scholar]
  14. Behrens O., Kohlhaw K., Günter H., Wonigeit K., Niesert S. Nachweis von Cyclosporin A in der Muttermilch--ist Stillen kontraindiziert? Geburtshilfe Frauenheilkd. 1989 Feb;49(2):207–209. doi: 10.1055/s-2008-1026581. [DOI] [PubMed] [Google Scholar]
  15. Bekesi J. G., Holland J. F., Anderson H. A., Fischbein A. S., Rom W., Wolff M. S., Selikoff I. J. Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls. Science. 1978 Mar 17;199(4334):1207–1209. doi: 10.1126/science.204005. [DOI] [PubMed] [Google Scholar]
  16. Berenbaum M. C. Time-dependence and selectivity of immunosuppressive agents. Immunology. 1979 Feb;36(2):355–365. [PMC free article] [PubMed] [Google Scholar]
  17. Blair J. T., Thomson A. W., Whiting P. H., Davidson R. J., Simpson J. G. Toxicity of the immune suppressant cyclosporin A in the rat. J Pathol. 1982 Oct;138(2):163–178. doi: 10.1002/path.1711380206. [DOI] [PubMed] [Google Scholar]
  18. Blaylock B. L., Holladay S. D., Comment C. E., Heindel J. J., Luster M. I. Exposure to tetrachlorodibenzo-p-dioxin (TCDD) alters fetal thymocyte maturation. Toxicol Appl Pharmacol. 1992 Feb;112(2):207–213. doi: 10.1016/0041-008x(92)90189-y. [DOI] [PubMed] [Google Scholar]
  19. Bluestone J. A., Pardoll D., Sharrow S. O., Fowlkes B. J. Characterization of murine thymocytes with CD3-associated T-cell receptor structures. Nature. 1987 Mar 5;326(6108):82–84. doi: 10.1038/326082a0. [DOI] [PubMed] [Google Scholar]
  20. Boorman G. A., Luster M. I., Dean J. H., Wilson R. E. The effect of adult exposure to diethylstilbestrol in the mouse on macrophage function and numbers. J Reticuloendothel Soc. 1980 Dec;28(6):547–560. [PubMed] [Google Scholar]
  21. Buchanan N. M., Khamashta M. A., Morton K. E., Kerslake S., Baguley E. A., Hughes G. R. A study of 100 high risk lupus pregnancies. Am J Reprod Immunol. 1992 Oct-Dec;28(3-4):192–194. doi: 10.1111/j.1600-0897.1992.tb00789.x. [DOI] [PubMed] [Google Scholar]
  22. Bunce J. V., Mason D. W. A spleen-thymus interaction is involved in the tolerization of thymocytes to xenogeneic erythrocytes. Eur J Immunol. 1983 Jan;13(1):85–87. doi: 10.1002/eji.1830130118. [DOI] [PubMed] [Google Scholar]
  23. Bung P., Molitor D. Pregnancy and postpartum after kidney transplantation and cyclosporin therapy--review of the literature adding a new case. J Perinat Med. 1991;19(5):397–401. doi: 10.1515/jpme.1991.19.5.397. [DOI] [PubMed] [Google Scholar]
  24. Burchiel S. W., Melmon K. L. Augmentation of the in vitro humoral immune response by pharmacologic agents. II: comparison of the effects of antiproliferative agents with DBcAMP. Immunopharmacology. 1979 Mar;1(2):151–163. doi: 10.1016/0162-3109(79)90051-1. [DOI] [PubMed] [Google Scholar]
  25. Chandra R. K. Immunocompetence in undernutrition. J Pediatr. 1972 Dec;81(6):1194–1200. doi: 10.1016/s0022-3476(72)80262-2. [DOI] [PubMed] [Google Scholar]
  26. Chapin R. E., Sloane R. A. Reproductive assessment by continuous breeding: evolving study design and summaries of ninety studies. Environ Health Perspect. 1997 Feb;105 (Suppl 1):199–205. doi: 10.1289/ehp.97105s1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Chen S., Golemboski K. A., Sanders F. S., Dietert R. R. Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune function and lead-induced immunotoxicity. Toxicology. 1999 Jan 1;132(1):67–79. doi: 10.1016/s0300-483x(98)00139-5. [DOI] [PubMed] [Google Scholar]
  28. Cockburn I., Krupp P., Monka C. Present experience of Sandimmun in pregnancy. Transplant Proc. 1989 Aug;21(4):3730–3732. [PubMed] [Google Scholar]
  29. Coté C. J., Meuwissen H. J., Pickering R. J. Effects on the neonate of prednisone and azathioprine administered to the mother during pregnancy. J Pediatr. 1974 Sep;85(3):324–328. doi: 10.1016/s0022-3476(74)80109-5. [DOI] [PubMed] [Google Scholar]
  30. Das S. N., Paul B. N., Saxena A. K., Ray P. K. Effect of in utero exposure to hexachlorocyclohexane on the developing immune system of mice. Immunopharmacol Immunotoxicol. 1990;12(2):293–310. doi: 10.3109/08923979009019674. [DOI] [PubMed] [Google Scholar]
  31. Datta N. Infection caused by Proteus mirabilis strains with transferrable gentamicin-resistance factors. Lancet. 1975 Jun 21;1(7921):1355–1357. doi: 10.1016/s0140-6736(75)92262-x. [DOI] [PubMed] [Google Scholar]
  32. Davis C. A., Vallota E. H., Forristal J. Serum complement levels in infancy: age related changes. Pediatr Res. 1979 Sep;13(9):1043–1046. doi: 10.1203/00006450-197909000-00019. [DOI] [PubMed] [Google Scholar]
  33. DeWys W. D., Goldin A., Man, El N. Hematopoietic recovery after large doses of cyclophosphamide: correlation of proliferative state with sensitivity. Cancer Res. 1970 Jun;30(6):1692–1697. [PubMed] [Google Scholar]
  34. Dean J. H., Padarathsingh M. L., Jerrells T. R., Keys L., Northing J. W. Assessment of immunobiological effects induced by chemicals, drugs or food additives. II. Studies with cyclophosphamide. Drug Chem Toxicol. 1979;2(1-2):133–153. doi: 10.3109/01480547908993186. [DOI] [PubMed] [Google Scholar]
  35. Dencker L., Hassoun E., d'Argy R., Alm G. Fetal thymus organ culture as an in vitro model for the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners. Mol Pharmacol. 1985 Jan;27(1):133–140. [PubMed] [Google Scholar]
  36. Dickneite G., Schorlemmer H. U., Racenberg J., Sedlacek H. H. Administration schedule of 15-deoxyspergualin and combination therapy with cyclosporin A in rat tail skin transplantation. Transplant Proc. 1989 Feb;21(1 Pt 1):1097–1098. [PubMed] [Google Scholar]
  37. Dieperink H., Steinbrüchel D., Kemp E., Svendsen P., Starklint H. Cataractogenic effect of cyclosporin A: a new adverse effect observed in the rat. Nephrol Dial Transplant. 1987;1(4):251–253. [PubMed] [Google Scholar]
  38. Djeu J. Y., Heinbaugh J. A., Vieira W. D., Holden H. T., Herberman R. B. The effect of immunopharmacological agents on mouse natural cell-mediated cytotoxicity and on its augmentation by poly I:C. Immunopharmacology. 1979 Jun;1(3):231–244. doi: 10.1016/0162-3109(79)90040-7. [DOI] [PubMed] [Google Scholar]
  39. EITZMAN D. V., SMITH R. T. The nonspecific inflammatory cycle in the neonatal infant. AMA J Dis Child. 1959 Mar;97(3):326–334. doi: 10.1001/archpedi.1959.02070010328011. [DOI] [PubMed] [Google Scholar]
  40. Faith R. E., Luster M. I., Kimmel C. A. Effect of chronic developmental lead exposure on cell-mediated immune functions. Clin Exp Immunol. 1979 Mar;35(3):413–420. [PMC free article] [PubMed] [Google Scholar]
  41. Faith R. E., Moore J. A. Impairment of thymus-dependent immune functions by exposure of the developing immune system to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). J Toxicol Environ Health. 1977 Oct;3(3):451–464. doi: 10.1080/15287397709529578. [DOI] [PubMed] [Google Scholar]
  42. Farber E. M., Nall L. Pustular psoriasis. Cutis. 1993 Jan;51(1):29–32. [PubMed] [Google Scholar]
  43. Farley D. E., Shelby J., Alexander D., Scott J. R. The effect of two new immunosuppressive agents, FK506 and didemnin B, in murine pregnancy. Transplantation. 1991 Jul;52(1):106–110. doi: 10.1097/00007890-199107000-00022. [DOI] [PubMed] [Google Scholar]
  44. Figliomeni M. L., Turkall R. M. Developmental immunotoxicity of cocaine and ethanol in postnatal Lewis rats. Immunopharmacology. 1997 Apr;36(1):41–48. doi: 10.1016/s0162-3109(96)00153-1. [DOI] [PubMed] [Google Scholar]
  45. Fine J. S., Gasiewicz T. A., Silverstone A. E. Lymphocyte stem cell alterations following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mol Pharmacol. 1989 Jan;35(1):18–25. [PubMed] [Google Scholar]
  46. Ford C. D., Johnson G. H., Smith W. G. Natural killer cells in in utero diethylstilbesterol-exposed patients. Gynecol Oncol. 1983 Dec;16(3):400–404. doi: 10.1016/0090-8258(83)90168-3. [DOI] [PubMed] [Google Scholar]
  47. Fried W., Tichler T., Dennenberg I., Barone J., Wang F. Effects of estrogens on hematopoietic stem cells and on hematopoiesis of mice. J Lab Clin Med. 1974 May;83(5):807–815. [PubMed] [Google Scholar]
  48. Gathings W. E., Kubagawa H., Cooper M. D. A distinctive pattern of B cell immaturity in perinatal humans. Immunol Rev. 1981;57:107–126. doi: 10.1111/j.1600-065x.1981.tb00444.x. [DOI] [PubMed] [Google Scholar]
  49. Gehrs B. C., Riddle M. M., Williams W. C., Smialowicz R. J. Alterations in the developing immune system of the F344 rat after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: II. Effects on the pup and the adult. Toxicology. 1997 Oct 19;122(3):229–240. doi: 10.1016/s0300-483x(97)00099-1. [DOI] [PubMed] [Google Scholar]
  50. Gehrs B. C., Smialowicz R. J. Alterations in the developing immune system of the F344 rat after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin I. [correction of II]. Effects on the fetus and the neonate. Toxicology. 1997 Oct 19;122(3):219–228. doi: 10.1016/s0300-483x(97)00098-x. [DOI] [PubMed] [Google Scholar]
  51. Gehrs B. C., Smialowicz R. J. Persistent suppression of delayed-type hypersensitivity in adult F344 rats after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicology. 1999 May 3;134(1):79–88. doi: 10.1016/s0300-483x(99)00024-4. [DOI] [PubMed] [Google Scholar]
  52. Glick B. Morphological changes and humoral immunity in cyclophosphamide-treated chicks. Transplantation. 1971 May;11(5):433–439. doi: 10.1097/00007890-197105000-00001. [DOI] [PubMed] [Google Scholar]
  53. Granelli-Piperno A. Lymphokine gene expression in vivo is inhibited by cyclosporin A. J Exp Med. 1990 Feb 1;171(2):533–544. doi: 10.1084/jem.171.2.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Greenman D. L., Dooley K., Breeden C. R. Strain differences in the response of the mouse to diethylstilbestrol. J Toxicol Environ Health. 1977 Oct;3(3):589–597. doi: 10.1080/15287397709529591. [DOI] [PubMed] [Google Scholar]
  55. Günter H., Frei U., Niesert S. Schwangerschaften nach Nierentransplantation und unter Immunsuppression mit Cyclosporin A. Geburtshilfe Frauenheilkd. 1989 Feb;49(2):155–159. doi: 10.1055/s-2008-1026567. [DOI] [PubMed] [Google Scholar]
  56. Hardin J. A., Hinoshita F., Sherr D. H. Mechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis. Toxicol Appl Pharmacol. 1992 Dec;117(2):155–164. doi: 10.1016/0041-008x(92)90232-h. [DOI] [PubMed] [Google Scholar]
  57. Hardy R. R., Carmack C. E., Shinton S. A., Kemp J. D., Hayakawa K. Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J Exp Med. 1991 May 1;173(5):1213–1225. doi: 10.1084/jem.173.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Hardy R. R., Hayakawa K. A developmental switch in B lymphopoiesis. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11550–11554. doi: 10.1073/pnas.88.24.11550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Hayakawa K., Tarlinton D., Hardy R. R. Absence of MHC class II expression distinguishes fetal from adult B lymphopoiesis in mice. J Immunol. 1994 May 15;152(10):4801–4807. [PubMed] [Google Scholar]
  60. Heeg K., Bendigs S., Wagner H. Cyclosporine A prevents the generation of single positive (Lyt2+ L3T4-, Lyt2- L3T4+) mature T cells, but not single positive (Lyt2+ T3-) Immature thymocytes, in newborn mice. Scand J Immunol. 1989 Dec;30(6):703–710. doi: 10.1111/j.1365-3083.1989.tb02479.x. [DOI] [PubMed] [Google Scholar]
  61. Hess A. D., Fischer A. C., Beschorner W. E. Effector mechanisms in cyclosporine A-induced syngeneic graft-versus-host disease. Role of CD4+ and CD8+ T lymphocyte subsets. J Immunol. 1990 Jul 15;145(2):526–533. [PubMed] [Google Scholar]
  62. Holladay S. D., Lindstrom P., Blaylock B. L., Comment C. E., Germolec D. R., Heindell J. J., Luster M. I. Perinatal thymocyte antigen expression and postnatal immune development altered by gestational exposure to tetrachlorodibenzo-p-dioxin (TCDD). Teratology. 1991 Oct;44(4):385–393. doi: 10.1002/tera.1420440405. [DOI] [PubMed] [Google Scholar]
  63. Holladay S. D. Prenatal immunotoxicant exposure and postnatal autoimmune disease. Environ Health Perspect. 1999 Oct;107 (Suppl 5):687–691. doi: 10.1289/ehp.99107s5687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Holladay S. D., Smith B. J. Alterations in murine fetal thymus and liver hematopoietic cell populations following developmental exposure to 7,12-dimethylbenz[a]anthracene. Environ Res. 1995 Feb;68(2):106–113. doi: 10.1006/enrs.1995.1014. [DOI] [PubMed] [Google Scholar]
  65. Holladay S. D., Smith B. J. Fetal hematopoietic alterations after maternal exposure to benzo[a]pyrene: a cytometric evaluation. J Toxicol Environ Health. 1994 Jul;42(3):259–273. doi: 10.1080/15287399409531878. [DOI] [PubMed] [Google Scholar]
  66. Houssaint E., Hallet M. M. Inability of adult circulating haemopoietic stem cells to sustain haemopoiesis in mouse fetal liver microenvironment. Immunology. 1988 Jul;64(3):463–467. [PMC free article] [PubMed] [Google Scholar]
  67. Howard S. K., Werner P. R., Sleight S. D. Polybrominated biphenyl toxicosis in swine: Effects on some aspects of the immune system in lactating sows and their offspring. Toxicol Appl Pharmacol. 1980 Aug;55(1):146–153. doi: 10.1016/0041-008x(80)90230-6. [DOI] [PubMed] [Google Scholar]
  68. Husmann L. A., Shimonkevitz R. P., Crispe I. N., Bevan M. J. Thymocyte subpopulations during early fetal development in the BALB/c mouse. J Immunol. 1988 Aug 1;141(3):736–740. [PubMed] [Google Scholar]
  69. Jenkins M. K., Schwartz R. H., Pardoll D. M. Effects of cyclosporine A on T cell development and clonal deletion. Science. 1988 Sep 23;241(4873):1655–1658. doi: 10.1126/science.241.4873.1655. [DOI] [PubMed] [Google Scholar]
  70. KAY H. E., PLAYFAIR J. H., WOLFENDALE M., HOPPER P. K. Development of the thymus in the human foetus and its relation to immunological potential. Nature. 1962 Oct 20;196:238–240. doi: 10.1038/196238a0. [DOI] [PubMed] [Google Scholar]
  71. Kalland T. Alterations of antibody response in female mice after neonatal exposure to diethylstilbestrol. J Immunol. 1980 Jan;124(1):194–198. [PubMed] [Google Scholar]
  72. Kalland T., Forsberg J. G. Natural killer cell activity and tumor susceptibility in female mice treated neonatally with diethylstilbestrol. Cancer Res. 1981 Dec;41(12 Pt 1):5134–5140. [PubMed] [Google Scholar]
  73. Kalland T., Fossberg T. M., Forsberg J. G. Effect of estrogen and corticosterone on the lymphoid system in neonatal mice. Exp Mol Pathol. 1978 Feb;28(1):76–95. doi: 10.1016/0014-4800(78)90066-7. [DOI] [PubMed] [Google Scholar]
  74. Kalland T. Ovarian influence on mitogen responsiveness of lymphocytes from mice neonatally exposed to diethylstilbestrol. J Toxicol Environ Health. 1980 Jan;6(1):67–74. doi: 10.1080/15287398009529831. [DOI] [PubMed] [Google Scholar]
  75. Kalland T. Reduced natural killer activity in female mice after neonatal exposure to diethylstilbestrol. J Immunol. 1980 Mar;124(3):1297–1300. [PubMed] [Google Scholar]
  76. Klintmalm G., Althoff P., Appleby G., Segerbrandt E. Renal function in a newborn baby delivered of a renal transplant patient taking cyclosporine. Transplantation. 1984 Aug;38(2):198–199. [PubMed] [Google Scholar]
  77. Kosugi A., Sharrow S. O., Shearer G. M. Effect of cyclosporin A on lymphopoiesis. I. Absence of mature T cells in thymus and periphery of bone marrow transplanted mice treated with cyclosporin A. J Immunol. 1989 May 1;142(9):3026–3032. [PubMed] [Google Scholar]
  78. Le Douarin N. M., Dieterlen-Lièvre F., Oliver P. D. Ontogeny of primary lymphoid organs and lymphoid stem cells. Am J Anat. 1984 Jul;170(3):261–299. doi: 10.1002/aja.1001700305. [DOI] [PubMed] [Google Scholar]
  79. Lerman S. P., Weidanz W. P. The effect of cyclophosphamide on the ontogeny of the humoral immune response in chickens. J Immunol. 1970 Sep;105(3):614–619. [PubMed] [Google Scholar]
  80. Lewis G. J., Lamont C. A., Lee H. A., Slapak M. Successful pregnancy in a renal transplant recipient taking cyclosporin A. Br Med J (Clin Res Ed) 1983 Feb 19;286(6365):603–603. doi: 10.1136/bmj.286.6365.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Liakopoulou A., Buttar H. S., Nera E. A., Fernando L. Effects of in utero exposure to cyclophosphamide in mice. II. Assessment of immunocompetence of offspring from 5 to 10 weeks of age. Immunopharmacol Immunotoxicol. 1989;11(2-3):193–209. doi: 10.3109/08923978909005365. [DOI] [PubMed] [Google Scholar]
  82. Lobach D. F., Haynes B. F. Ontogeny of the human thymus during fetal development. J Clin Immunol. 1987 Mar;7(2):81–97. doi: 10.1007/BF00916002. [DOI] [PubMed] [Google Scholar]
  83. Lower G. D., Stevens L. E., Najarian J. S., Reemtsma K. Problems from immunosuppressives during pregnancy. Am J Obstet Gynecol. 1971 Dec 15;111(8):1120–1121. doi: 10.1016/0002-9378(71)90115-3. [DOI] [PubMed] [Google Scholar]
  84. Luebke R. W., Riddle M. M., Rogers R. R., Garner R. J., Rowe D. G., Smialowicz R. J. Immune function of young adult mice following in utero exposure to cyclophosphamide. J Toxicol Environ Health. 1986;18(1):25–39. doi: 10.1080/15287398609530845. [DOI] [PubMed] [Google Scholar]
  85. Luster M. I., Blank J. A., Dean J. H. Molecular and cellular basis of chemically induced immunotoxicity. Annu Rev Pharmacol Toxicol. 1987;27:23–49. doi: 10.1146/annurev.pa.27.040187.000323. [DOI] [PubMed] [Google Scholar]
  86. Luster M. I., Dean J. H., Boorman G. A., Archer D. L., Lauer L., Lawson L. D., Moore J. A., Wilson R. E. The effects of orthophenylphenol, tris(2,3-dichloropropyl) phosphate, and cyclophosphamide on the immune system and host susceptibility of mice following subchronic exposure. Toxicol Appl Pharmacol. 1981 Apr;58(2):252–261. doi: 10.1016/0041-008x(81)90430-0. [DOI] [PubMed] [Google Scholar]
  87. Luster M. I., Faith R. E., Clark G. Laboratory studies on the immune effects of halogenated aromatics. Ann N Y Acad Sci. 1979 May 31;320:473–486. doi: 10.1111/j.1749-6632.1979.tb56628.x. [DOI] [PubMed] [Google Scholar]
  88. Luster M. I., Faith R. E., McLachlan J. A. Alterations of the antibody response following in utero exposure to diethylstilbestrol. Bull Environ Contam Toxicol. 1978 Oct;20(4):433–437. doi: 10.1007/BF01683543. [DOI] [PubMed] [Google Scholar]
  89. Many A., Pauzner R., Carp H., Langevitz P., Martinowitz U. Treatment of patients with antiphospholipid antibodies during pregnancy. Am J Reprod Immunol. 1992 Oct-Dec;28(3-4):216–218. doi: 10.1111/j.1600-0897.1992.tb00795.x. [DOI] [PubMed] [Google Scholar]
  90. Markowitz J., Grancher K., Mandel F., Daum F. Immunosuppressive therapy in pediatric inflammatory bowel disease: results of a survey of the North American Society for Pediatric Gastroenterology and Nutrition. Subcommittee on Immunosuppressive Use of the Pediatric IBD Collaborative Research Forum. Am J Gastroenterol. 1993 Jan;88(1):44–48. [PubMed] [Google Scholar]
  91. Mattsson R., Mattsson A., Kihlström J. E., Lindahl-Kiessling K. Effects of a hexachlorinated biphenyl on lymphoid organs and resorption of foetuses in pregnant mice. Arch Environ Contam Toxicol. 1981;10(3):281–288. doi: 10.1007/BF01055629. [DOI] [PubMed] [Google Scholar]
  92. Milbrath D. S., Engel J. L., Verkade J. G., Casida J. E. Structure--toxicity relationships of 1-substituted-4-alkyl-2,6,7-trioxabicyclo[2.2.2.]octanes. Toxicol Appl Pharmacol. 1979 Feb;47(2):287–293. doi: 10.1016/0041-008x(79)90323-5. [DOI] [PubMed] [Google Scholar]
  93. Miller T. E., Golemboski K. A., Ha R. S., Bunn T., Sanders F. S., Dietert R. R. Developmental exposure to lead causes persistent immunotoxicity in Fischer 344 rats. Toxicol Sci. 1998 Apr;42(2):129–135. doi: 10.1006/toxs.1998.2424. [DOI] [PubMed] [Google Scholar]
  94. Misra R. R., Bloom S. E. Roles of dosage, pharmacokinetics, and cellular sensitivity to damage in the selective toxicity of cyclophosphamide towards B and T cells in development. Toxicology. 1991 Mar 11;66(3):239–256. doi: 10.1016/0300-483x(91)90196-8. [DOI] [PubMed] [Google Scholar]
  95. Miyawaki T., Moriya N., Nagaoki T., Taniguchi N. Maturation of B-cell differentiation ability and T-cell regulatory function in infancy and childhood. Immunol Rev. 1981;57:61–87. doi: 10.1111/j.1600-065x.1981.tb00442.x. [DOI] [PubMed] [Google Scholar]
  96. Montgomery D. W., Zukoski C. F. Didemnin B: a new immunosuppressive cyclic peptide with potent activity in vitro and in vivo. Transplantation. 1985 Jul;40(1):49–56. [PubMed] [Google Scholar]
  97. Mudzinski S. P. Effects of benzo[a]pyrene on concanavalin A-stimulated human peripheral blood mononuclear cells in vitro: inhibition of proliferation but no effect on parameters related to the G1 phase of the cell cycle. Toxicol Appl Pharmacol. 1993 Apr;119(2):166–174. doi: 10.1006/taap.1993.1057. [DOI] [PubMed] [Google Scholar]
  98. Mumford D. M., Sung J. S., Wallis J. O., Kaufman R. H. The lymphocyte transformation response of fetal hemolymphatic tissue to mitogens and antigens. Pediatr Res. 1978 Mar;12(3):171–175. doi: 10.1203/00006450-197803000-00002. [DOI] [PubMed] [Google Scholar]
  99. NICOL T., BILBEY D. L., CHARLES L. M., CORDINGLEY J. L., VERNON-ROBERTS B. OESTROGEN: THE NATURAL STIMULANT OF BODY DEFENCE. J Endocrinol. 1964 Oct;30:277–291. doi: 10.1677/joe.0.0300277. [DOI] [PubMed] [Google Scholar]
  100. Nandakumaran M., Eldeen A. S. Transfer of cyclosporine in the perfused human placenta. Dev Pharmacol Ther. 1990;15(2):101–105. doi: 10.1159/000457628. [DOI] [PubMed] [Google Scholar]
  101. Noller K. L., Blair P. B., O'Brien P. C., Melton L. J., 3rd, Offord J. R., Kaufman R. H., Colton T. Increased occurrence of autoimmune disease among women exposed in utero to diethylstilbestrol. Fertil Steril. 1988 Jun;49(6):1080–1082. doi: 10.1016/s0015-0282(16)59965-8. [DOI] [PubMed] [Google Scholar]
  102. Olson L. J., Hsia M. T., Kreamer B. L., Hinsdill R. D. Immunosuppression in weanling and adult Sprague-Dawley rats induced by acute exposure to 3,3',4,4'-tetrachloroazoxybenzene. Toxicology. 1984 Sep 28;32(4):287–296. doi: 10.1016/0300-483x(84)90081-7. [DOI] [PubMed] [Google Scholar]
  103. Owen J. J., Raff M. C. Studies on the differentiation of thymus-derived lymphocytes. J Exp Med. 1970 Dec 1;132(6):1216–1232. doi: 10.1084/jem.132.6.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Pabelick C., Kemmer F., Koletzko B. Befunde bei Neugeborenen nierentransplantierter Mütter. Monatsschr Kinderheilkd. 1991 Mar;139(3):136–140. [PubMed] [Google Scholar]
  105. Pardoll D. M., Fowlkes B. J., Bluestone J. A., Kruisbeek A., Maloy W. L., Coligan J. E., Schwartz R. H. Differential expression of two distinct T-cell receptors during thymocyte development. Nature. 1987 Mar 5;326(6108):79–81. doi: 10.1038/326079a0. [DOI] [PubMed] [Google Scholar]
  106. Penit C., Vasseur F. Cell proliferation and differentiation in the fetal and early postnatal mouse thymus. J Immunol. 1989 May 15;142(10):3369–3377. [PubMed] [Google Scholar]
  107. Pickrell M. D., Sawers R., Michael J. Pregnancy after renal transplantation: severe intrauterine growth retardation during treatment with cyclosporin A. Br Med J (Clin Res Ed) 1988 Mar 19;296(6625):825–825. doi: 10.1136/bmj.296.6625.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Pinto-Machado J. Influence of prenatal administration of busulfan on the postnatal development of mice. Production of a syndrome including hypoplasia of the thymus. Teratology. 1970 Nov;3(4):363–370. doi: 10.1002/tera.1420030413. [DOI] [PubMed] [Google Scholar]
  109. Poland A., Knutson J. C. 2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annu Rev Pharmacol Toxicol. 1982;22:517–554. doi: 10.1146/annurev.pa.22.040182.002505. [DOI] [PubMed] [Google Scholar]
  110. Ptachcinski R. J., Burckart G. J., Venkataramanan R. Cyclosporine. Drug Intell Clin Pharm. 1985 Feb;19(2):90–100. doi: 10.1177/106002808501900202. [DOI] [PubMed] [Google Scholar]
  111. Reznik V. M., Jones K. L., Durham B. L., Mendoza S. A. Changes in facial appearance during cyclosporin treatment. Lancet. 1987 Jun 20;1(8547):1405–1407. doi: 10.1016/s0140-6736(87)90595-2. [DOI] [PubMed] [Google Scholar]
  112. Ridge J. P., Fuchs E. J., Matzinger P. Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. Science. 1996 Mar 22;271(5256):1723–1726. doi: 10.1126/science.271.5256.1723. [DOI] [PubMed] [Google Scholar]
  113. Ryffel B., Donatsch P., Madörin M., Matter B. E., Rüttimann G., Schön H., Stoll R., Wilson J. Toxicological evaluation of cyclosporin A. Arch Toxicol. 1983 Jun;53(2):107–141. doi: 10.1007/BF00302721. [DOI] [PubMed] [Google Scholar]
  114. SCHLESINGER M., MARK R. WASTING DISEASE INDUCED IN YOUNG MICE BY ADMINISTRATION OF CORTISOL ACETATE. Science. 1964 Feb 28;143(3609):965–966. doi: 10.1126/science.143.3609.965. [DOI] [PubMed] [Google Scholar]
  115. Safe S. Polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs): biochemistry, toxicology, and mechanism of action. Crit Rev Toxicol. 1984;13(4):319–395. doi: 10.3109/10408448409023762. [DOI] [PubMed] [Google Scholar]
  116. Sakaguchi S., Sakaguchi N. Organ-specific autoimmune disease induced in mice by elimination of T cell subsets. V. Neonatal administration of cyclosporin A causes autoimmune disease. J Immunol. 1989 Jan 15;142(2):471–480. [PubMed] [Google Scholar]
  117. Salhab A. S., James M. O., Wang S. L., Shiverick K. T. Formation of benzo[a]pyrene-DNA adducts by microsomal enzymes: comparison of maternal and fetal liver, fetal hematopoietic cells and placenta. Chem Biol Interact. 1987 Mar;61(3):203–214. doi: 10.1016/0009-2797(87)90001-9. [DOI] [PubMed] [Google Scholar]
  118. Schubert G., Stoffregen C., Loske G., Timmermann W., Schang T., Thiede A. Synergistic effect of 15-deoxyspergualin and cyclosporin A in pancreatic transplantation. Transplant Proc. 1989 Feb;21(1 Pt 1):1096–1096. [PubMed] [Google Scholar]
  119. Schuit K. E., DeBiasio R. Kinetics of phagocyte response to group B streptococcal infections in newborn rats. Infect Immun. 1980 May;28(2):319–324. doi: 10.1128/iai.28.2.319-324.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  120. Seaman W. E., Merigan T. C., Talal N. Natural killing in estrogen-treated mice responds poorly to poly I.C despite normal stimulation of circulating interferon. J Immunol. 1979 Dec;123(6):2903–2905. [PubMed] [Google Scholar]
  121. Smialowicz R. J., Riddle M. M., Rogers R. R., Rowe D. G., Luebke R. W., Fogelson L. D., Copeland C. B. Immunologic effects of perinatal exposure of rats to dioctyltin dichloride. J Toxicol Environ Health. 1988;25(4):403–422. doi: 10.1080/15287398809531220. [DOI] [PubMed] [Google Scholar]
  122. Spyker-Cranmer J. M., Barnett J. B., Avery D. L., Cranmer M. F. Immunoteratology of chlordane: cell-mediated and humoral immune responses in adult mice exposed in utero. Toxicol Appl Pharmacol. 1982 Mar 15;62(3):402–408. doi: 10.1016/0041-008x(82)90141-7. [DOI] [PubMed] [Google Scholar]
  123. Stites D. P., Carr M. C., Fudenberg H. H. Ontogeny of cellular immunity in the human fetus: development of responses to phytohemagglutinin and to allogeneic cells. Cell Immunol. 1974 Mar 30;11(1-3):257–271. doi: 10.1016/0008-8749(74)90026-4. [DOI] [PubMed] [Google Scholar]
  124. THORBECKE G. J. Some histological and functional aspects of lymphoid tissue in germfree animals. I. Morphological studies. Ann N Y Acad Sci. 1959 May 8;78:237–246. doi: 10.1111/j.1749-6632.1959.tb53106.x. [DOI] [PubMed] [Google Scholar]
  125. Takagi Y., Aburada S., Otake T., Ikegami N. Effect of polychlorinated biphenyls (PCBs) accumulated in the dam's body on mouse filial immunocompetence. Arch Environ Contam Toxicol. 1987 May;16(3):375–381. doi: 10.1007/BF01054956. [DOI] [PubMed] [Google Scholar]
  126. Talcott P. A., Koller L. D. The effect of inorganic lead and/or a polychlorinated biphenyl on the developing immune system of mice. J Toxicol Environ Health. 1983 Aug-Sep;12(2-3):337–352. doi: 10.1080/15287398309530431. [DOI] [PubMed] [Google Scholar]
  127. Tavassoli M. Embryonic and fetal hemopoiesis: an overview. Blood Cells. 1991;17(2):269–286. [PubMed] [Google Scholar]
  128. Tentori L., Pardoll D. M., Zuñiga J. C., Hu-Li J., Paul W. E., Bluestone J. A., Kruisbeek A. M. Proliferation and production of IL-2 and B cell stimulatory factor 1/IL-4 in early fetal thymocytes by activation through Thy-1 and CD3. J Immunol. 1988 Feb 15;140(4):1089–1094. [PubMed] [Google Scholar]
  129. Tincani A., Faden D., Tarantini M., Lojacono A., Tanzi P., Gastaldi A., Di Mario C., Spatola L., Cattaneo R., Balestrieri G. Systemic lupus erythematosus and pregnancy: a prospective study. Clin Exp Rheumatol. 1992 Sep-Oct;10(5):439–446. [PubMed] [Google Scholar]
  130. Toivanen P., Uksila J., Leino A., Lassila O., Hirvonen T., Ruuskanen O. Development of mitogen responding T cells and natural killer cells in the human fetus. Immunol Rev. 1981;57:89–105. doi: 10.1111/j.1600-065x.1981.tb00443.x. [DOI] [PubMed] [Google Scholar]
  131. Tsurumi H., Tani K., Tsuruta T., Shirato R., Matsudaira T., Tojo A., Wada C., Uchida H., Ozawa K., Asano S. Adult T-cell leukemia developing during immunosuppressive treatment in a renal transplant recipient. Am J Hematol. 1992 Dec;41(4):292–294. doi: 10.1002/ajh.2830410414. [DOI] [PubMed] [Google Scholar]
  132. Tydén G., Brattström C., Björkman U., Landgraf R., Baltzer J., Hillebrand G., Land W., Calne R., Brons I. G., Squifflet J. P. Pregnancy after combined pancreas-kidney transplantation. Diabetes. 1989 Jan;38 (Suppl 1):43–45. doi: 10.2337/diab.38.1.s43. [DOI] [PubMed] [Google Scholar]
  133. Ulrich R., Levy L., Kasson B., Harwick H. J., Brammer G. Developmental changes of immunoglobulins in rats treated neonatally with hydrocortisone. Proc Soc Exp Biol Med. 1977 Jan;154(1):107–111. doi: 10.3181/00379727-154-39614. [DOI] [PubMed] [Google Scholar]
  134. Urso P., Gengozian N. Alterations in the humoral immune response and tumor frequencies in mice exposed to benzo[a]pyrene and X-rays before or after birth. J Toxicol Environ Health. 1982 Oct-Nov;10(4-5):817–835. doi: 10.1080/15287398209530297. [DOI] [PubMed] [Google Scholar]
  135. Urso P., Gengozian N. Subnormal expression of cell-mediated and humoral immune responses in progeny disposed toward a high incidence of tumors after in utero exposure to benzo[a]pyrene. J Toxicol Environ Health. 1984;14(4):569–584. doi: 10.1080/15287398409530606. [DOI] [PubMed] [Google Scholar]
  136. Urso P., Johnson R. A. Early changes in T lymphocytes and subsets of mouse progeny defective as adults in controlling growth of a syngeneic tumor after in utero insult with benzo(a)pyrene. Immunopharmacology. 1987 Sep;14(1):1–10. doi: 10.1016/0162-3109(87)90003-8. [DOI] [PubMed] [Google Scholar]
  137. Velardi A., Cooper M. D. An immunofluorescence analysis of the ontogeny of myeloid, T, and B lineage cells in mouse hemopoietic tissues. J Immunol. 1984 Aug;133(2):672–677. [PubMed] [Google Scholar]
  138. Ville Y., Fernandez H., Samuel D., Bismuth H., Frydman R. La grossesse après transplantation hépatique. A propos de 17 grossesses. J Gynecol Obstet Biol Reprod (Paris) 1992;21(6):691–696. [PubMed] [Google Scholar]
  139. Vos J. G., Moore J. A. Suppression of cellular immunity in rats and mice by maternal treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Int Arch Allergy Appl Immunol. 1974;47(5):777–794. doi: 10.1159/000231268. [DOI] [PubMed] [Google Scholar]
  140. Walker S. E., Keisler L. W., Caldwell C. W., Kier A. B., vom Saal F. S. Effects of altered prenatal hormonal environment on expression of autoimmune disease in NZB/NZW mice. Environ Health Perspect. 1996 Aug;104 (Suppl 4):815–821. doi: 10.1289/ehp.96104s4815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  141. Warner N. L., Uhr J. W., Thorbecke G. J., Ovary Z. Immunoglobulins, antibodies and the bursa of Fabricus: induction of agammaglobulinemia and the loss of all antibody-forming capacity by hormonal bursectomy. J Immunol. 1969 Dec;103(6):1317–1330. [PubMed] [Google Scholar]
  142. Watson R. R., Haffer K. Modifications of cell-mediated immune responses by moderate dietary protein stress in immunologically immature and mature BALB/c mice. Mech Ageing Dev. 1980 Mar;12(3):269–278. doi: 10.1016/0047-6374(80)90050-0. [DOI] [PubMed] [Google Scholar]
  143. Ways S. C., Blair P. B., Bern H. A., Staskawicz M. O. Immune responsiveness of adult mice exposed neonatally to diethylstilbestrol, steroid hormones, or vitamin A. J Environ Pathol Toxicol. 1980 Jun-Jul;3(5-6):207–220. [PubMed] [Google Scholar]
  144. Ways S. C., Mortola J. F., Zvaifler N. J., Weiss R. J., Yen S. S. Alterations in immune responsiveness in women exposed to diethylstilbestrol in utero. Fertil Steril. 1987 Aug;48(2):193–197. doi: 10.1016/s0015-0282(16)59341-8. [DOI] [PubMed] [Google Scholar]
  145. Weber H., Birnbaum L. S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) in pregnant C57BL/6N mice: distribution to the embryo and excretion. Arch Toxicol. 1985 Aug;57(3):159–162. doi: 10.1007/BF00290880. [DOI] [PubMed] [Google Scholar]
  146. Wilson C. B. Immunologic basis for increased susceptibility of the neonate to infection. J Pediatr. 1986 Jan;108(1):1–12. doi: 10.1016/s0022-3476(86)80761-2. [DOI] [PubMed] [Google Scholar]
  147. Wingard D. L., Turiel J. Long-term effects of exposure to diethylstilbestrol. West J Med. 1988 Nov;149(5):551–554. [PMC free article] [PubMed] [Google Scholar]
  148. Wunderlich V., Tetzlaff I. Applikation von 3H-Benzo(a)pyren an gravide Mäuse und Ratten: Inkorporation der Radioaktivität in subzelluläre Fraktionen verschiedener Gewebe. Arch Geschwulstforsch. 1973;42(2):95–106. [PubMed] [Google Scholar]
  149. Zacharchuk C. M., Merćep M., Ashwell J. D. Thymocyte activation and death: a mechanism for molding the T cell repertoire. Ann N Y Acad Sci. 1991 Dec 30;636:52–70. doi: 10.1111/j.1749-6632.1991.tb33438.x. [DOI] [PubMed] [Google Scholar]
  150. d'Argy R., Dencker L., Klasson-Wehler E., Bergman A., Darnerud P. O., Brandt I. 3,3'4,4'-Tetrachlorobiphenyl in pregnant mice: embryotoxicity, teratogenicity, and toxic effects on the cultured embryonic thymus. Pharmacol Toxicol. 1987 Jul;61(1):53–57. doi: 10.1111/j.1600-0773.1987.tb01772.x. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES