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. 1983 Nov;72(5):1629–1638. doi: 10.1172/JCI111122

Depression of the lymphocyte transformation response to microbial antigens and to phytohemagglutinin during pregnancy.

R C Brunham, D H Martin, T W Hubbard, C C Kuo, C W Critchlow, L D Cles, D A Eschenbach, K K Holmes
PMCID: PMC370451  PMID: 6355182

Abstract

Lymphocyte transformation (LT) responses to Chlamydia trachomatis, to four other microbial antigens, and to phytohemagglutinin (PHA) were studied in 201 women during pregnancy and/or 3-18 wk postpartum. The LT responses to all stimulants tested were significantly depressed during pregnancy when compared with postpartum LT responses. This difference occurred whether LT assays were performed in autologous or pooled heterologous plasma collected from nonpregnant donors. Among women studied in the third trimester and again postpartum, the autologous LT stimulation index (LTSI) rose from 1.7 to 3.4 (P less than 0.001) with C. trachomatis elementary body antigen, from 3.7 to 7.9 (P less than 0.001) with Candida albicans cell wall extract, from 4.5 to 7.8 (P = 0.008) with streptokinase-streptodornase, from 1.7 to 3.0 (P = 0.007) with fluid tetanus toxoid, from 1.7 to 2.8 (P = 0.046) with mumps virus skin test antigen, from 35.5 to 87.0 (P less than 0.001) with PHA (2 micrograms/ml), and from 107.2 to 181.9 (P = 0.007) with PHA (10 micrograms/ml). LT responses to C. trachomatis were compared in 52 pregnant women and 58 nonpregnant women; all the women had C. trachomatis isolated at the time of LT assay. Using either plasma supplement, the mean LTSI with C. trachomatis antigen was significantly higher in nonpregnant women than in pregnant women, regardless of trimester (P less than 0.001). Among 12 women who were serially tested and remained culture positive for C. trachomatis throughout pregnancy and the postpartum period, the mean autologous LTSI rose from 1.9 in the third trimester to 7.8 postpartum (P = 0.0004). These data are the first to show that the immune response to an ongoing bacterial infection is depressed during pregnancy and to definitively document the depressed LT responses during human pregnancy.

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Selected References

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  1. Anderson D. J. The responsiveness of various maternal mouse lymphocyte populations to mitogenic stimulation in vitro. Cell Immunol. 1978 Nov;41(1):150–156. doi: 10.1016/s0008-8749(78)80034-3. [DOI] [PubMed] [Google Scholar]
  2. Birkeland S. A., Kristoffersen K. Cellular immunity in pregnancy: blast transformation and rosette formation of maternal T and B lymphocytes: A cross-section analysis. Clin Exp Immunol. 1977 Dec;30(3):408–412. [PMC free article] [PubMed] [Google Scholar]
  3. Bissenden J. G., Ling N. R., Mackintosh P. Suppression of mixed lymphocyte reactions by pregnancy serum. Clin Exp Immunol. 1980 Jan;39(1):195–202. [PMC free article] [PubMed] [Google Scholar]
  4. Bjune G., Barnetson R. S., Ridley D. S., Kronvall G. Lymphocyte transformation test in leprosy; correlation of the response with inflammation of lesions. Clin Exp Immunol. 1976 Jul;25(1):85–94. [PMC free article] [PubMed] [Google Scholar]
  5. Brunham R. C., Martin D. H., Kuo C. C., Wang S. P., Stevens C. E., Hubbard T., Holmes K. K. Cellular immune response during uncomplicated genital infection with Chlamydia trachomatis in humans. Infect Immun. 1981 Oct;34(1):98–104. doi: 10.1128/iai.34.1.98-104.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  7. Carr M. C., Stites D. P., Fudenberg H. H. Cellular immune aspects of the human fetal maternal relationship. II. In vitro response of gravida lymphocytes to phytohemagglutinin. Cell Immunol. 1973 Sep;8(3):448–454. doi: 10.1016/0008-8749(73)90136-6. [DOI] [PubMed] [Google Scholar]
  8. Covelli H. D., Wilson R. T. Immunologic and medical considerations in tuberculin-sensitized pregnant patients. Am J Obstet Gynecol. 1978 Oct 1;132(3):256–259. doi: 10.1016/0002-9378(78)90889-x. [DOI] [PubMed] [Google Scholar]
  9. Duncan M. E., Melsom R., Pearson J. M., Ridley D. S. The association of pregnancy and leprosy. I. New cases, relapse of cured patients and deterioration in patients on treatment during pregnancy and lactation--results of a prospective study of 154 pregnancies in 147 Ethiopian women. Lepr Rev. 1981 Sep;52(3):245–262. doi: 10.5935/0305-7518.19810035. [DOI] [PubMed] [Google Scholar]
  10. Finn R., St Hill C. A., Govan A. J., Ralfs I. G., Gurney F. J., Denye V. Immunological responses in pregnancy and survival of fetal homograft. Br Med J. 1972 Jul 15;3(5819):150–152. doi: 10.1136/bmj.3.5819.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fujisaki S., Mori N., Sasaki T., Maeyama M. Cell-mediated immunity in human pregnancy: Changes in lymphocyte reactivity during pregnancy and postpartum. Microbiol Immunol. 1979;23(9):899–907. doi: 10.1111/j.1348-0421.1979.tb02823.x. [DOI] [PubMed] [Google Scholar]
  12. GREENBERG M., JACOBZINER H., PAKTER J., WEISL B. A. Maternal mortality in the epidemic of Asian influenza, New York City, 1957. Am J Obstet Gynecol. 1958 Oct;76(4):897–902. doi: 10.1016/0002-9378(58)90027-9. [DOI] [PubMed] [Google Scholar]
  13. Gehrz R. C., Christianson W. R., Linner K. M., Conroy M. M., McCue S. A., Balfour H. H., Jr A longitudinal analysis of lymphocyte proliferative responses to mitogens and antigens during human pregnancy. Am J Obstet Gynecol. 1981 Jul 15;140(6):665–670. doi: 10.1016/0002-9378(81)90201-5. [DOI] [PubMed] [Google Scholar]
  14. Gilles H. M., Lawson J. B., Sibelas M., Voller A., Allan N. Malaria, anaemia and pregnancy. Ann Trop Med Parasitol. 1969 Jun;63(2):245–263. doi: 10.1080/00034983.1969.11686625. [DOI] [PubMed] [Google Scholar]
  15. Hammarström L., Fuchs T., Smith C. I. The immunodepressive effect of human glucoproteins and their possible role in the nonrejection process during pregnancy. Acta Obstet Gynecol Scand. 1979;58(5):417–422. doi: 10.3109/00016347909154059. [DOI] [PubMed] [Google Scholar]
  16. Harrison M. R. Maternal immunocompetence. II. Proliferative responses of maternal lymphocytes in vitro and inhibition by serum from pregnant rats. Scand J Immunol. 1976;5(8):881–889. doi: 10.1111/j.1365-3083.1976.tb03038.x. [DOI] [PubMed] [Google Scholar]
  17. Hill C. A., Finn R., Denye V. Depression of cellular immunity in pregnancy due to a serum factor. Br Med J. 1973 Sep 8;3(5879):513–514. doi: 10.1136/bmj.3.5879.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hsu C. C. Peripheral blood lymphocyte responses to phytohemagglutinin and pokeweed mitogen during pregnancy. Proc Soc Exp Biol Med. 1974 Jul;146(3):771–775. doi: 10.3181/00379727-146-38190. [DOI] [PubMed] [Google Scholar]
  19. Kasakura S. A factor in maternal plasma during pregnancy that suppresses the reactivity of mixed leukocyte cultures. J Immunol. 1971 Nov;107(5):1296–1301. [PubMed] [Google Scholar]
  20. Khuroo M. S., Teli M. R., Skidmore S., Sofi M. A., Khuroo M. I. Incidence and severity of viral hepatitis in pregnancy. Am J Med. 1981 Feb;70(2):252–255. doi: 10.1016/0002-9343(81)90758-0. [DOI] [PubMed] [Google Scholar]
  21. Kuo C., Wang S., Wentworth B. B., Grayston J. T. Primary isolation of TRIC organisms in HeLa 229 cells treated with DEAE-dextran. J Infect Dis. 1972 Jun;125(6):665–668. doi: 10.1093/infdis/125.6.665. [DOI] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Marolis G. B., Buckley R. H., Younger J. B. Serum immunogbulin cocentrations during normal pregnancy. Am J Obstet Gynecol. 1971 Apr 1;109(7):971–976. doi: 10.1016/0002-9378(71)90275-4. [DOI] [PubMed] [Google Scholar]
  24. McIntyre J. A., Faulk W. P. Maternal blocking factors in human pregnancy are found in plasma not serum. Lancet. 1979 Oct 20;2(8147):821–823. doi: 10.1016/s0140-6736(79)92176-7. [DOI] [PubMed] [Google Scholar]
  25. Murray D. L., Imagawa D. T., Okada D. M., St Geme J. W., Jr Antibody response to monovalent A/New Jersey/8/76 influenza vaccine in pregnant women. J Clin Microbiol. 1979 Aug;10(2):184–187. doi: 10.1128/jcm.10.2.184-187.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Noonan F. P., Halliday W. J., Morton H., Clunie G. J. Early pregnancy factor is immunosuppressive. Nature. 1979 Apr 12;278(5705):649–651. doi: 10.1038/278649a0. [DOI] [PubMed] [Google Scholar]
  27. Okamura K., Kuramoto M., Hamazaki Y., Takahashi K., Suzuki M. Immunosuppressive factors in pregnancy serum: a preliminary report. Tohoku J Exp Med. 1980 Jan;130(1):11–23. doi: 10.1620/tjem.130.11. [DOI] [PubMed] [Google Scholar]
  28. Pavia C. S., Stites D. P. Humoral and cellular regulation of alloimmunity in pregnancy. J Immunol. 1979 Nov;123(5):2194–2200. [PubMed] [Google Scholar]
  29. Petrucco O. M., Seamark R. F., Holmes K., Forbes I. J., Symons R. G. Changes in lymphocyte function during pregnancy. Br J Obstet Gynaecol. 1976 Mar;83(3):245–250. doi: 10.1111/j.1471-0528.1976.tb00818.x. [DOI] [PubMed] [Google Scholar]
  30. Poskitt P. K., Kurt E. A., Paul B. B., Selvaraj R. J., Sbarra A. J., Mitchell G. W., Jr Response to mitogen during pregnancy and the postpartum period. Obstet Gynecol. 1977 Sep;50(3):319–323. [PubMed] [Google Scholar]
  31. RAO A. R., PRAHLAD I., SWAMINATHAN M., LAKSHMI A. Pregnancy and smallpox. J Indian Med Assoc. 1963 Apr 16;40:353–363. [PubMed] [Google Scholar]
  32. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. SIEGEL M., GREENBERG M. Incidence of poliomyelitis in pregnancy; its relation to maternal age, parity and gestational period. N Engl J Med. 1955 Nov 17;253(20):841–847. doi: 10.1056/NEJM195511172532001. [DOI] [PubMed] [Google Scholar]
  34. Sridama V., Pacini F., Yang S. L., Moawad A., Reilly M., DeGroot L. J. Decreased levels of helper T cells: a possible cause of immunodeficiency in pregnancy. N Engl J Med. 1982 Aug 5;307(6):352–356. doi: 10.1056/NEJM198208053070606. [DOI] [PubMed] [Google Scholar]
  35. Suzuki K., Tomasi T. B., Jr Immune responses during pregnancy. Evidence of suppressor cells for splenic antibody response. J Exp Med. 1979 Oct 1;150(4):898–908. doi: 10.1084/jem.150.4.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Thong Y. H., Steele R. W., Vincent M. M., Hensen S. A., Bellanti J. A. Impaired in vitro cell-mediated immunity to rubella virus during pregnancy. N Engl J Med. 1973 Sep 20;289(12):604–606. doi: 10.1056/NEJM197309202891203. [DOI] [PubMed] [Google Scholar]
  37. Tomoda Y., Fuma M., Miwa T., Saiki N., Ishizuka N. Cell-mediated immunity in pregnant women. Gynecol Invest. 1976;7(5):280–292. doi: 10.1159/000301389. [DOI] [PubMed] [Google Scholar]
  38. VAUGHAN J. E., RAMIREZ H. Coccidioidomycosis as a complication of pregnancy. Calif Med. 1951 Feb;74(2):121–125. [PMC free article] [PubMed] [Google Scholar]
  39. Wang S. P., Grayston J. T. Human serology in Chlamydia trachomatis infection with microimmunofluorescence. J Infect Dis. 1974 Oct;130(4):388–397. doi: 10.1093/infdis/130.4.388. [DOI] [PubMed] [Google Scholar]
  40. Wentworth B. B., Alexander E. R. Isolation of Chlamydia trachomatis by use of 5-iodo-2-deoxyuridine-treated cells. Appl Microbiol. 1974 May;27(5):912–916. doi: 10.1128/am.27.5.912-916.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Yamamoto T., Hirata H., Taniguchi H., Kawai Y., Uematsu A., Sugiyama Y. Lymphocyte transformation during pregnancy: an analysis using whole-blood culture. Obstet Gynecol. 1980 Feb;55(2):215–219. [PubMed] [Google Scholar]
  42. Yoder B. L., Stamm W. E., Koester C. M., Alexander E. R. Microtest procedure for isolation of Chlamydia trachomatis. J Clin Microbiol. 1981 Jun;13(6):1036–1039. doi: 10.1128/jcm.13.6.1036-1039.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

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