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. 1981 Dec 1;154(6):1922–1934. doi: 10.1084/jem.154.6.1922

Protection against graft vs. host-associated immunosuppression in F1 mice. I. Activation of F1 regulatory cells by host-specific anti-major histocompatibility complex antibodies

PMCID: PMC2186549  PMID: 7320686

Abstract

Injection of parental spleen cells into unirradiated F1 hybrid mice results in suppression of the potential to generate cytotoxic T lymphocyte (CTL) responses in vitro. In an attempt to protect the F1 mice from immunosuppression, the recipients were injected with antibodies specific for major histocompatibility complex (MHC)-encoded antigens of the F1 mice 24 h before inoculation of the parental spleen cells. 8-14 d later, the generation of CTL responses in vitro against H- 2 alloantigens was tested. Alloantiserum directed against either parental haplotype of the F1 strain markedly diminished the suppression of CTL activity. Furthermore, monoclonal antibodies recognizing H-2 or Ia antigens protected the F2 mice from parental spleen cell-induced suppression. Although this study has been limited to reagents that recognize host H-2 determinants, these findings do not necessarily imply that protection against graft vs. host (GvH) can be achieved only with anti-MHC antibodies. However, protection was observed only by antibodies reactive with F1 antigens, and small amounts of the alloantibodies were sufficient to diminish CTL suppression. Adoptive transfer of spleen cells from syngeneic F1 mice treated with anti-h-2a alloantiserum 24 h previously provided protection equal to that of injection of the recipients with alloantibodies. The cells necessary for this effect were shown to be T cells and to be radiosensitive to 2000 rad. This cell population is induced by antisera against F1 cell surface antigens and effectively counteracts GvH-associated immuno- suppression.

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Selected References

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

  1. BATCHELOR J. R., HOWARD J. G. SYNERGIC AND ANTAGONISTIC EFFECTS OF ISOANTIBODY UPON GRAFT-VERSUS-HOST DISEASE. Transplantation. 1965 Mar;3:161–169. doi: 10.1097/00007890-196503000-00004. [DOI] [PubMed] [Google Scholar]
  2. Bellgrau D., Wilson D. B. Immunological studies of T-cell receptors. I. Specifically induced resistance to graft-versus-host disease in rats mediated by host T-cell immunity to alloreactive parental T cells. J Exp Med. 1978 Jul 1;148(1):103–114. doi: 10.1084/jem.148.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Binz H., Lindenmann J., Wigzell H. Inhibition of local graft-versus-host reaction by anti-alloantibodies. Nature. 1973 Nov 16;246(5429):146–148. doi: 10.1038/246146a0. [DOI] [PubMed] [Google Scholar]
  4. Cazenave P. A. Idiotypic-anti-idiotypic regulation of antibody synthesis in rabbits. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5122–5125. doi: 10.1073/pnas.74.11.5122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Elkins W. L. Cellular immunology and the pathogenesis of graft versus host reactions. Prog Allergy. 1971;15:78–187. [PubMed] [Google Scholar]
  6. Gershon R. K., Eardley D. D., Durum S., Green D. R., Shen F. W., Yamauchi K., Cantor H., Murphy D. B. Contrasuppression. A novel immunoregulatory activity. J Exp Med. 1981 Jun 1;153(6):1533–1546. doi: 10.1084/jem.153.6.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Glucksberg H., Storb R., Fefer A., Buckner C. D., Neiman P. E., Clift R. A., Lerner K. G., Thomas E. D. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974 Oct;18(4):295–304. doi: 10.1097/00007890-197410000-00001. [DOI] [PubMed] [Google Scholar]
  8. Grebe S. C., Streilein J. W. Graft-versus-Host reactions: a review. Adv Immunol. 1976;22:119–221. doi: 10.1016/s0065-2776(08)60549-0. [DOI] [PubMed] [Google Scholar]
  9. Jerne N. K. The somatic generation of immune recognition. Eur J Immunol. 1971 Jan;1(1):1–9. doi: 10.1002/eji.1830010102. [DOI] [PubMed] [Google Scholar]
  10. Jose D. G., Stutman O., Good R. A. Inhibition of graft-versus-host reactions in mice by host-directed antibody. Effect of serum dose and immunoglobulin subclass. Transplantation. 1974 Feb;17(2):211–215. doi: 10.1097/00007890-197402000-00009. [DOI] [PubMed] [Google Scholar]
  11. Katz D. H., Osborne D. P., Jr The allogeneic effect in inbred mice. II. Establishment of the cellular interactions required for enhancement of antibody production by the graft-versus-host reaction. J Exp Med. 1972 Sep 1;136(3):455–465. doi: 10.1084/jem.136.3.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. McKearn T. J., Hamada Y., Stuart F. P., Fitch F. W. Anti-receptor antibody and resistance to graft-versus-host disease. Nature. 1974 Oct 18;251(5476):648–650. doi: 10.1038/251648a0. [DOI] [PubMed] [Google Scholar]
  14. Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Safford J. W., Jr, Tokuda S. Suppression of the graft-versus-host reaction by passive immunization of donor against recipient antigens. Proc Soc Exp Biol Med. 1970 Feb;133(2):651–654. doi: 10.3181/00379727-133-34537. [DOI] [PubMed] [Google Scholar]
  18. Schmitt-Verhulst A. M., Pettinelli C. B., Henkart P. A., Lunney J. K., Shearer G. M. H-2-restricted cytotoxic effectors generated in vitro by the addition of trinitrophenyl-conjugated soluble proteins. J Exp Med. 1978 Feb 1;147(2):352–368. doi: 10.1084/jem.147.2.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Streilein J. W., Stone M. J., Duncan W. R. Studies on the specificity of autoantibodies produced in systemic graft-vs-host disease. J Immunol. 1975 Jan;114(1 Pt 2):255–260. [PubMed] [Google Scholar]
  21. Thomas E., Storb R., Clift R. A., Fefer A., Johnson F. L., Neiman P. E., Lerner K. G., Glucksberg H., Buckner C. D. Bone-marrow transplantation (first of two parts). N Engl J Med. 1975 Apr 17;292(16):832–843. doi: 10.1056/NEJM197504172921605. [DOI] [PubMed] [Google Scholar]
  22. Voisin G. A., Kinsky R. G., Maillard J. Réativité immunitaire et anticorps facilitants chez des animaux tolérants aux homogreffes. Ann Inst Pasteur (Paris) 1968 Nov;115(5):855–879. [PubMed] [Google Scholar]

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