Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Mar 1;157(3):936–946. doi: 10.1084/jem.157.3.936

Graft-vs.-host-associated immune suppression is activated by recognition of allogeneic murine I-A antigens

PMCID: PMC2186963  PMID: 6403650

Abstract

Several combinations of F1 hybrid mice were injected intravenously with parental spleen cells to determine the minimal H-2 differences between F1 and parent that are necessary to induce graft-vs.-host-associated immune suppression (GVH-associated suppression). 7-14 d after injection, the spleens of the F1 mice were tested for cytotoxic T lymphocyte potential by in vitro sensitization against trinitrophenyl- self and H-2 alloantigens. The results indicate that parental T lymphocytes must recognize I-A allogeneic determinants of the F1 recipient in order to induce suppression. Recognition of K or D alone or D with I region products other than I-A did not induce suppression. The recognition of I region without K and/or D and even the I-A difference between C57BL/6 and the B6.Cbm12 mutation resulted in immune suppression that was as potent as that resulting from the recognition of K, D, and I together. The possible significance of this function for I-A antigens is discussed with respect to three clinical examples of immune suppression for which this phenomenon may be relevant.

Full Text

The Full Text of this article is available as a PDF (774.5 KB).

Selected References

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

  1. Fathman C. G., Kimoto M., Melvold R., David C. S. Reconstitution of Ir genes, Ia antigens, and mixed lymphocyte reaction determinants by gene complementation. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1853–1857. doi: 10.1073/pnas.78.3.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Goyert S. M., Shively J. E., Silver J. Biochemical characterization of a second family of human Ia molecules, HLA-DS, equivalent to murine I-A subregion molecules. J Exp Med. 1982 Aug 1;156(2):550–566. doi: 10.1084/jem.156.2.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Groopman J. E., Gottlieb M. S. Kaposi's sarcoma: an oncologic looking glass. Nature. 1982 Sep 9;299(5879):103–104. doi: 10.1038/299103a0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Hamilton B. L., Parkman R. Kinetics of the anti-recipient cytotoxic cell response of mice with minor histocompatibility antigen graft-vs-host disease. J Immunol. 1982 Jan;128(1):376–379. [PubMed] [Google Scholar]
  6. Hamilton J. R., Overall J. C., Glasgow L. A. Synergistic effect on mortality in mice with murine cytomegalovirus and Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections. Infect Immun. 1976 Oct;14(4):982–989. doi: 10.1128/iai.14.4.982-989.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hurley C. K., Shaw S., Nadler L., Schlossman S., Capra J. D. Alpha and beta chains of SB and DR antigens are structurally distinct. J Exp Med. 1982 Nov 1;156(5):1557–1562. doi: 10.1084/jem.156.5.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hurtenbach U., Sachs D. H., Shearer G. M. Protection against graft vs. host-associated immunosuppression in F1 mice. I. Activation of F1 regulatory cells by host-specific anti-major histocompatibility complex antibodies. J Exp Med. 1981 Dec 1;154(6):1922–1934. doi: 10.1084/jem.154.6.1922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hurtenbach U., Shearer G. M. Germ cell-induced immune suppression in mice. Effect of inoculation of syngeneic spermatozoa on cell-mediated immune responses. J Exp Med. 1982 Jun 1;155(6):1719–1729. doi: 10.1084/jem.155.6.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klein J., Chiang C. L. Ability of H-2 regions to induce graft-vs-host disease. J Immunol. 1976 Sep;117(3):736–740. [PubMed] [Google Scholar]
  11. Lafuse W. P., McCormick J. F., Melvold R. W., David C. S. Serological and biochemical analysis of Ia molecules in the I-A mutant B6.C-H-2. Transplantation. 1981 Jun;31(6):434–438. doi: 10.1097/00007890-198106000-00006. [DOI] [PubMed] [Google Scholar]
  12. Lee D. R., Hansen T. H., Cullen S. E. Detection of an altered I-A beta polypeptide in the murine Ir mutant, B6.C-h-2bm12. J Immunol. 1982 Jul;129(1):245–251. [PubMed] [Google Scholar]
  13. Levy R. B., Shearer G. M. Regulation of T-cell-mediated lympholysis by the murine major histocompatibility complex. I. Preferential in vitro responses to trinitrophenyl-modified self K- and D-coded gene products in parental and F1 hybrid mouse strains. J Exp Med. 1979 Jun 1;149(6):1379–1392. doi: 10.1084/jem.149.6.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Masur H., Michelis M. A., Greene J. B., Onorato I., Stouwe R. A., Holzman R. S., Wormser G., Brettman L., Lange M., Murray H. W. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med. 1981 Dec 10;305(24):1431–1438. doi: 10.1056/NEJM198112103052402. [DOI] [PubMed] [Google Scholar]
  15. McKenzie I. F., Morgan G. M., Sandrin M. S., Michaelides M. M., Melvold R. W., Kohn H. I. B6.C-H-2bm12. A new H-2 mutation in the I region in the mouse. J Exp Med. 1979 Dec 1;150(6):1323–1338. doi: 10.1084/jem.150.6.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oppltová L., Démant P. Genetic determinants for the graft-vs.-host reaction in the H-2 complex. Transplant Proc. 1973 Dec;5(4):1367–1371. [PubMed] [Google Scholar]
  17. Parkman R., Rappeport J., Rosen F. Human graft versus host disease. J Invest Dermatol. 1980 May;74(5):276–279. doi: 10.1111/1523-1747.ep12543412. [DOI] [PubMed] [Google Scholar]
  18. Pickel K., Hoffmann M. K. Suppressor T cells arising in mice undergoing a graft-vs-host response. J Immunol. 1977 Feb;118(2):653–656. [PubMed] [Google Scholar]
  19. Pollack M. S., Kirkpatrick D., Kapoor N., Dupont B., O'Reilly R. J. Identification by HLA typing of intrauterine-derived maternal T cells in four patients with severe combined immunodeficiency. N Engl J Med. 1982 Sep 9;307(11):662–666. doi: 10.1056/NEJM198209093071106. [DOI] [PubMed] [Google Scholar]
  20. Prud'homme G. J., Sohn U., Delovitch T. L. The role of H-2 and Ia antigens in graft-versus-host reactions (GVHR). Presence of host alloantigens on donor cells after GVHR and suppression of GVHR with an anti-Ia antiserum against hose Ia antigens. J Exp Med. 1979 Jan 1;149(1):137–149. doi: 10.1084/jem.149.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shand F. L. Analysis of immunosuppression generated by the graft-versus-host reaction. II. Characterization of the suppression cell and its mechanism of action. Immunology. 1976 Dec;31(6):943–951. [PMC free article] [PubMed] [Google Scholar]
  22. Shearer G. M., Polisson R. P. Mutual recognition of parental and F lymphocytes. III. Parental determinants recognized by F host mice in resistance to graft-vs-host-associated immunosuppression map to H-2Db. J Immunol. 1981 Feb;126(2):545–547. [PubMed] [Google Scholar]
  23. Shearer G. M., Polisson R. P. Mutual recognition of parental and F1 lymphocytes. Selective abrogation of cytotoxic potential of F1 lymphocytes by parental lymphocytes. J Exp Med. 1980 Jan 1;151(1):20–31. doi: 10.1084/jem.151.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shulman H. M., Sullivan K. M., Weiden P. L., McDonald G. B., Striker G. E., Sale G. E., Hackman R., Tsoi M. S., Storb R., Thomas E. D. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980 Aug;69(2):204–217. doi: 10.1016/0002-9343(80)90380-0. [DOI] [PubMed] [Google Scholar]
  25. Siegal F. P., Lopez C., Hammer G. S., Brown A. E., Kornfeld S. J., Gold J., Hassett J., Hirschman S. Z., Cunningham-Rundles C., Adelsberg B. R. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med. 1981 Dec 10;305(24):1439–1444. doi: 10.1056/NEJM198112103052403. [DOI] [PubMed] [Google Scholar]
  26. de Waal L. P., Melief C. J., Melvold R. W. Cytotoxic T lymphocytes generated across and I-Ab mutant difference are directed against a molecule bearing Ia antigens. Eur J Immunol. 1981 Mar;11(3):258–265. doi: 10.1002/eji.1830110317. [DOI] [PubMed] [Google Scholar]
  27. van Rappard-van der Veen F. M., Rolink A. G., Gleichmann E. Diseases caused by reactions of T lymphocytes towards incompatible structures of the major histocompatibility complex. VI. Autoantibodies characteristic of systemic lupus erythematosus induced by abnormal T-B cell cooperation across I-E. J Exp Med. 1982 May 1;155(5):1555–1560. doi: 10.1084/jem.155.5.1555. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES