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. 1987 Jun 1;165(6):1552–1564. doi: 10.1084/jem.165.6.1552

Variable capacity of L3T4+ T cells to cause lethal graft-versus-host disease across minor histocompatibility barriers in mice

PMCID: PMC2188361  PMID: 3108446

Abstract

Highly purified populations of L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to cause lethal GVHD in six different H-2- compatible, multiple minor histocompatibility antigen-different murine strain combinations. In four of these combinations (C3H.SW----B6, DBA/2- ---B10.D2, B10.BR----CBA, and B10.S----SJL), lethal GVHD appeared to be caused almost entirely by Lyt-2+ cells; the injection of L3T4+ cells resulted in low mortality even when these cells were presensitized to the recipient antigens. In the remaining two combinations (B10.D2---- DBA/2 and B10.D2----BALB/c), L3T4+ T cells were able to cause a high incidence of GVHD and were more potent than the Lyt-2+ cells. The implications of these findings are discussed.

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Selected References

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  1. Ferrara J. L., Marion A., McIntyre J. F., Murphy G. F., Burakoff S. J. Amelioration of acute graft vs host disease due to minor histocompatibility antigens by in vivo administration of anti-interleukin 2 receptor antibody. J Immunol. 1986 Sep 15;137(6):1874–1877. [PubMed] [Google Scholar]
  2. Golding H., Munitz T. I., Singer A. Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity. J Exp Med. 1985 Sep 1;162(3):943–961. doi: 10.1084/jem.162.3.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Goronzy J., Weyand C. M., Fathman C. G. Long-term humoral unresponsiveness in vivo, induced by treatment with monoclonal antibody against L3T4. J Exp Med. 1986 Sep 1;164(3):911–925. doi: 10.1084/jem.164.3.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Guy-Grand D., Vassalli P. Gut injury in mouse graft-versus-host reaction. Study of its occurrence and mechanisms. J Clin Invest. 1986 May;77(5):1584–1595. doi: 10.1172/JCI112474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Halle-Pannenko O., Pritchard L. L., Bruley-Rosset M., Berumen L., Motta R. Parameters involved in the induction and abrogation of the lethal graft-versus-host reaction directed against non-H-2 antigens. Immunol Rev. 1985 Dec;88:59–85. doi: 10.1111/j.1600-065x.1985.tb01153.x. [DOI] [PubMed] [Google Scholar]
  6. Halle-Pannenko O., Pritchard L. L., Motta R., Mathé G. Non-H-2 antigens can induce high GVH mortality in adult recipients of normal cells. Biomedicine. 1978 Nov;29(7):253–255. [PubMed] [Google Scholar]
  7. Hamilton B. L., Bevan M. J., Parkman R. Anti-recipient cytotoxic T lymphocyte precursors are present in the spleens of mice with acute graft versus host disease due to minor histocompatibility antigens. J Immunol. 1981 Feb;126(2):621–625. [PubMed] [Google Scholar]
  8. 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]
  9. Jadus M. R., Peck A. B. Lethal murine graft-versus-host disease in the absence of detectable cytotoxic T lymphocytes. Transplantation. 1983 Sep;36(3):281–289. doi: 10.1097/00007890-198309000-00011. [DOI] [PubMed] [Google Scholar]
  10. Johnson L. L., Bailey D. W., Mobraaten L. E. Antigenic competition between minor (non-H-2) histocompatibility antigens. Immunogenetics. 1981;13(5):451–455. doi: 10.1007/BF00346026. [DOI] [PubMed] [Google Scholar]
  11. Kelso A., Glasebrook A. L. Secretion of interleukin 2, macrophage-activating factor, interferon, and colony-stimulating factor by alloreactive T lymphocyte clones. J Immunol. 1984 Jun;132(6):2924–2931. [PubMed] [Google Scholar]
  12. Korngold R., Sprent J. Features of T cells causing H-2-restricted lethal graft-vs.-host disease across minor histocompatibility barriers. J Exp Med. 1982 Mar 1;155(3):872–883. doi: 10.1084/jem.155.3.872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Korngold R., Sprent J. Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow. J Exp Med. 1978 Dec 1;148(6):1687–1698. doi: 10.1084/jem.148.6.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Korngold R., Sprent J. Negative selection of T cells causing lethal graft-versus-host disease across minor histocompatibility barriers. Role of the H-2 complex. J Exp Med. 1980 May 1;151(5):1114–1124. doi: 10.1084/jem.151.5.1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Korngold R., Sprent J. Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences. J Immunol. 1985 Nov;135(5):3004–3010. [PubMed] [Google Scholar]
  16. Mowat A. M., Borland A., Parrott D. M. Hypersensitivity reactions in the small intestine. VII. Induction of the intestinal phase of murine graft-versus-host-reaction by Lyt 2- T cells activated by I-A alloantigens. Transplantation. 1986 Feb;41(2):192–198. [PubMed] [Google Scholar]
  17. Okunewick J. P., Meredith R. F., Raikow R. B., Buffo M. J., Jones D. L. Possibility of three distinct and separable components to fatal graft-vs-host reaction. Exp Hematol. 1982 Mar;10(3):277–291. [PubMed] [Google Scholar]
  18. Roopenian D. C., Widmer M. B., Orosz C. G., Bach F. H. Helper cell-independent cytolytic T lymphocytes specific for a minor histocompatibility antigen. J Immunol. 1983 Feb;130(2):542–545. [PubMed] [Google Scholar]
  19. Rosenberg A. S., Mizuochi T., Singer A. Analysis of T-cell subsets in rejection of Kb mutant skin allografts differing at class I MHC. 1986 Aug 28-Sep 3Nature. 322(6082):829–831. doi: 10.1038/322829a0. [DOI] [PubMed] [Google Scholar]
  20. Sprent J., Schaefer M., Lo D., Korngold R. Functions of purified L3T4+ and Lyt-2+ cells in vitro and in vivo. Immunol Rev. 1986 Jun;91:195–218. doi: 10.1111/j.1600-065x.1986.tb01489.x. [DOI] [PubMed] [Google Scholar]
  21. Sprent J., Schaefer M., Lo D., Korngold R. Properties of purified T cell subsets. II. In vivo responses to class I vs. class II H-2 differences. J Exp Med. 1986 Apr 1;163(4):998–1011. doi: 10.1084/jem.163.4.998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sprent J., Schaefer M. Properties of purified T cell subsets. I. In vitro responses to class I vs. class II H-2 alloantigens. J Exp Med. 1985 Dec 1;162(6):2068–2088. doi: 10.1084/jem.162.6.2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Vallera D. A., Soderling C. C., Kersey J. H. Bone marrow transplantation across major histocompatability barriers in mice. III. Treatment of donor grafts with monoclonal antibodies directed against Lyt determinants. J Immunol. 1982 Feb;128(2):871–875. [PubMed] [Google Scholar]
  24. Von Boehmer H., Turton K. Autonomously proliferating K/D-restricted cytolytic T cell clones. Eur J Immunol. 1983 Feb;13(2):176–179. doi: 10.1002/eji.1830130216. [DOI] [PubMed] [Google Scholar]
  25. Wettstein P. J., Bailey D. W. Immunodominance in the immune response to "multiple" histocompatibility antigens. Immunogenetics. 1982;16(1):47–58. doi: 10.1007/BF00364441. [DOI] [PubMed] [Google Scholar]
  26. Wettstein P. J., Frelinger J. A. T lymphocyte responses to non-H-2 histocompatibility antigens. I. Role of Ly-1+2+ T cells as cytotoxic effectors and requirement for Ly-1+2+ T cells for optimal generation of cytotoxic effectors. J Immunol. 1981 Jul;127(1):43–46. [PubMed] [Google Scholar]
  27. Wettstein P. J. Immunodominance in the T-cell response to multiple non-H-2 histocompatibility antigens. II. Observation of a hierarchy among dominant antigens. Immunogenetics. 1986;24(1):24–31. doi: 10.1007/BF00372294. [DOI] [PubMed] [Google Scholar]
  28. Widmer M. B., Bach F. H. Antigen-driven helper cell-independent cloned cytolytic T lymphocytes. Nature. 1981 Dec 24;294(5843):750–752. doi: 10.1038/294750a0. [DOI] [PubMed] [Google Scholar]
  29. von Boehmer H., Haas W. H-2 restricted cytolytic and noncytolytic T cell clones: isolation, specificity and functional analysis. Immunol Rev. 1981;54:27–56. doi: 10.1111/j.1600-065x.1981.tb00433.x. [DOI] [PubMed] [Google Scholar]
  30. von Boehmer H., Kisielow P., Leiserson W., Haas W. Lyt-2- T cell-independent functions of Lyt-2+ cells stimulated with antigen or concanavalin A. J Immunol. 1984 Jul;133(1):59–64. [PubMed] [Google Scholar]

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