Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1972 Jul 1;136(1):21–38. doi: 10.1084/jem.136.1.21

THE HOST CELL RESPONSE IN THE LOCAL GRAFT-VERSUS-HOST REACTION INDUCED IN THE KIDNEYS OF F1 RATS BY PARENTAL THORACIC DUCT LYMPHOCYTES

Alvin Volkman 1
PMCID: PMC2139187  PMID: 4402393

Abstract

Radioautographs of infiltrative cells in the kidneys of (Lewis x BN)F1 rats labeled with tritiated thymidine (TdR3H) before the subcapsular injection of parental (Lewis) thoracic duct lymphocytes (TDL) showed a predominantly host-proliferative response by 4 days after grafting. The immediate renal incorporation of TdR3H was used to measure the local graft-vs.-host (GVH) reactions. Substantial reactions could still be induced in the face of the considerable degree of leukopenia after 400 R whole body γ-irradiation. These results suggest that radioresistant cells are capable of carrying on the appropriate host activities and that the weakness of GVH reactions induced after higher doses of irradiation may be due to impairment of the mitotic mechanism of host cells. The importance of circulating leukocytes as a source of immunogenic stimulation was nevertheless substantiated by inducing local GVH reactions with Lew TDL in chimeric parental-type rats that had been repopulated with F1 bone marrow. This result also emphasizes the nonspecific nature of tissue destruction in the renal GVH reaction in confirmation of Elkins. In this and other situations in which B cells were the predominant F1 type elements available for interaction with parental-type TDL the reactions were nearly equivalent or equivalent to those in the appropriate controls. Typical local GVH reactions could be induced in heavily irradiated hosts by an inoculum of combined parental and F1-type TDL in the apparent absence of mononuclear phagocytes. The possible relationship between the activation of host lymphocytes, the involvement of B cells, and the nonspecific nature of tissue damage in the renal GVH is discussed.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Alter B. J., Bach F. H. Lymphocyte reactivity in vitro. I. Cellular reconstitution of purified lymphocyte response. Cell Immunol. 1970 Jul;1(2):207–218. doi: 10.1016/0008-8749(70)90008-0. [DOI] [PubMed] [Google Scholar]
  2. Cantor H., Asofsky R. Synergy among lymphoid cells mediating the graft-versus-host response. II. Synergy in graft-versus-host reactions produced by Balb-c lymphoid cells of differing anatomic origin. J Exp Med. 1970 Feb;131(2):235–246. doi: 10.1084/jem.131.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Claman H. N., Chaperon E. A. Immunologic complementation between thymus and marrow cells--a model for the two-cell theory of immunocompetence. Transplant Rev. 1969;1:92–113. doi: 10.1111/j.1600-065x.1969.tb00137.x. [DOI] [PubMed] [Google Scholar]
  4. Cline M. J., Swett V. C. The interaction of human monocytes and lymphocytes. J Exp Med. 1968 Dec 1;128(6):1309–1325. doi: 10.1084/jem.128.6.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen I. R., Feldman M. The lysis of fibroblasts by lymphocytes sensitized in vitro: specific antigen activates a nonspecific effect. Cell Immunol. 1970 Nov;1(5):521–535. doi: 10.1016/0008-8749(70)90039-0. [DOI] [PubMed] [Google Scholar]
  6. DAVIES A. J., DOAK S. M. Fate of homologous adult spleen cells injected into new-born mice. Nature. 1960 Aug 13;187:610–611. doi: 10.1038/187610b0. [DOI] [PubMed] [Google Scholar]
  7. Davies A. J. The thymus and the cellular basis of immunity. Transplant Rev. 1969;1:43–91. doi: 10.1111/j.1600-065x.1969.tb00136.x. [DOI] [PubMed] [Google Scholar]
  8. Davis W. E., Jr, Cole L. J., Schaffer W. T. Studies on synergistic thymus-bone marrow cell interactions in immunological responses. Proc Soc Exp Biol Med. 1970 Jan;133(1):144–150. doi: 10.3181/00379727-133-34427. [DOI] [PubMed] [Google Scholar]
  9. ELKINS W. L. INVASION AND DESTRUCTION OF HOMOLOGOUS KIDNEY BY LOCALLY INOCULATED LYMPHOID CELLS. J Exp Med. 1964 Sep 1;120:329–348. doi: 10.1084/jem.120.3.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Elkins W. L., Guttmann R. D. Pathogenesis of a local graft versus host reaction: immunogenicity of circulating host leukocytes. Science. 1968 Mar 15;159(3820):1250–1251. doi: 10.1126/science.159.3820.1250. [DOI] [PubMed] [Google Scholar]
  11. Elkins W. L. Specific and nonspecific lymphoid cell proliferation in the pathogenesis of graft-versus-host reactions. Transplantation. 1970 Mar;9(3):273–301. doi: 10.1097/00007890-197003000-00011. [DOI] [PubMed] [Google Scholar]
  12. Elkins W. L. The interaction of donor and host lymphoid cells in the pathogenesis of renal cortical destruction induced by a local graft versus host reaction. J Exp Med. 1966 Jan 1;123(1):103–118. doi: 10.1084/jem.123.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Elkins W. L. The sources of immunogenic stimulation of lymphoid cells mediating a local graft-versus-host reaction in rat kidney. Transplantation. 1971 Jun;11(6):551–560. [PubMed] [Google Scholar]
  14. FOX M. Cytological estimation of proliferating donor cells during graft-versus-host disease in F1 hybrid mice injected with parental spleen cells. Immunology. 1962 Jul;5:489–495. [PMC free article] [PubMed] [Google Scholar]
  15. Feldman J. D., Unanue E. R. Role of macrophages in delayed hypersensitivity. II. Effects of anti-macrophage antibody. Cell Immunol. 1971 Jun;2(3):275–282. doi: 10.1016/0008-8749(71)90047-5. [DOI] [PubMed] [Google Scholar]
  16. GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
  17. GOWANS J. L. The fate of parental strain small lymphocytes in F1 hybrid rats. Ann N Y Acad Sci. 1962 Oct 24;99:432–455. doi: 10.1111/j.1749-6632.1962.tb45326.x. [DOI] [PubMed] [Google Scholar]
  18. GOWANS J. L. The recirculation of lymphocytes from blood to lymph in the rat. J Physiol. 1959 Apr 23;146(1):54–69. doi: 10.1113/jphysiol.1959.sp006177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gordon J. Role of monocytes in the mixed leukocyte culture reaction. Proc Soc Exp Biol Med. 1968 Jan;127(1):30–33. doi: 10.3181/00379727-127-32613. [DOI] [PubMed] [Google Scholar]
  20. HOLM G., PERLMANN P., WERNER B. PHYTOHAEMAGGLUTININ-INDUCED CYTOTOXIC ACTION OF NORMAL LYMPHOID CELLS ON CELLS IN TISSUE CULTURE. Nature. 1964 Aug 22;203:841–843. doi: 10.1038/203841a0. [DOI] [PubMed] [Google Scholar]
  21. HOWARD J. G., MICHIE D., SIMONSEN M. Splenomegaly as a host response in graft-versus-host disease. Br J Exp Pathol. 1961 Oct;42:478–485. [PMC free article] [PubMed] [Google Scholar]
  22. Hilgard H. R. Synergism of thymus and bone marrow in the production of gra a5hilgard HR: Synergism of thymus and bone marrow in the production of graft-versus-host splenomegaly in x-irradiated hosts. J Exp Med. 1970 Aug 1;132(2):317–328. doi: 10.1084/jem.132.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Holm G., Perlmann P. Cytotoxic potential of stimulated human lymphocytes. J Exp Med. 1967 Apr 1;125(4):721–736. doi: 10.1084/jem.125.4.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Häyry P., Defendi V. Mixed lymphocyte cultures produce effector cells: model in vitro for allograft rejection. Science. 1970 Apr 3;168(3927):133–135. doi: 10.1126/science.168.3927.133. [DOI] [PubMed] [Google Scholar]
  25. KOSUNEN T. U., DVORAK H. F. The "transfer reaction" in the rabbit. II. A radioautographic study. Lab Invest. 1963 Jun;12:628–637. [PubMed] [Google Scholar]
  26. Miller J. F., Mitchell G. F. Thymus and antigen-reactive cells. Transplant Rev. 1969;1:3–42. doi: 10.1111/j.1600-065x.1969.tb00135.x. [DOI] [PubMed] [Google Scholar]
  27. Roitt I. M., Greaves M. F., Torrigiani G., Brostoff J., Playfair J. H. The cellular basis of immunological responses. A synthesis of some current views. Lancet. 1969 Aug 16;2(7616):367–371. doi: 10.1016/s0140-6736(69)92712-3. [DOI] [PubMed] [Google Scholar]
  28. Roman N., Perkins S. F., Perkins E. M., Jr, Dolnick E. H. Orcein-hematoxylin in iodized ferric chloride as a stain for elastic fibers, with metanil yellow counterstaining. Stain Technol. 1967 Jul;42(4):199–202. doi: 10.3109/10520296709115008. [DOI] [PubMed] [Google Scholar]
  29. SIMONSEN M. Graft versus host reactions. Their natural history, and applicability as tools of research. Prog Allergy. 1962;6:349–467. [PubMed] [Google Scholar]
  30. STROBER S., GOWANS J. L. THE ROLE OF LYMPHOCYTES IN THE SENSITIZATION OF RATS TO RENAL HOMOGRAFTS. J Exp Med. 1965 Aug 1;122:347–360. doi: 10.1084/jem.122.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sabbadini E. Studies on the mechanism of target cell lysis induced by immune cells. J Reticuloendothel Soc. 1970 May;7(5):551–566. [PubMed] [Google Scholar]
  32. Singh J. N., Sabbadini E., Sehon A. H. Nonspecific cytotoxicity in graft-versus-host reactions. Transplantation. 1971 May;11(5):475–478. doi: 10.1097/00007890-197105000-00008. [DOI] [PubMed] [Google Scholar]
  33. Stuttman O., Good R. A. Absence of synergism between thymus and bone marrow in graft-versus-host reactions. Proc Soc Exp Biol Med. 1969 Mar;130(3):848–852. doi: 10.3181/00379727-130-33670. [DOI] [PubMed] [Google Scholar]
  34. Svedmyr E. A., Hodes R. J. On the specificity of cell-mediated cytotoxicity in vitro. Cell Immunol. 1970 Dec;1(6):644–654. doi: 10.1016/0008-8749(70)90029-8. [DOI] [PubMed] [Google Scholar]
  35. Taylor R. B. Cellular cooperation in the antibody response of mice to two serum albumins: specific function of thymus cells. Transplant Rev. 1969;1:114–149. doi: 10.1111/j.1600-065x.1969.tb00138.x. [DOI] [PubMed] [Google Scholar]
  36. Tyan M. L. Fetal liver and adult thymus cells: absence of synergism in graft-versus-host reactions. Proc Soc Exp Biol Med. 1969 Dec;132(3):1183–1185. doi: 10.3181/00379727-132-34392. [DOI] [PubMed] [Google Scholar]
  37. Volkman A., Collins F. M. The restorative effect of peritoneal macrophages on delayed hypersensitivity following ionizing radiation. Cell Immunol. 1971 Dec;2(6):552–566. doi: 10.1016/0008-8749(71)90004-9. [DOI] [PubMed] [Google Scholar]
  38. Wilson D. B., Silvers W. K., Nowell P. C. Quantitative studies on the mixed lymphocyte interaction in rats. II. Relationship of the proliferative response to the immunologic status of the donors. J Exp Med. 1967 Oct 1;126(4):655–665. doi: 10.1084/jem.126.4.655. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES