Lethal graft-versus-host disease in mice directed to multiple minor histocompatibility antigens: features of CD8+ and CD4+ T cell responses.
Lethal graft-versus-host disease (GVHD) can be induced in MHC-matched strain combinations which differ in their expression of multiple minor histocompatibility (H) antigens. It has been shown that CD8+ T cells play an important role in the development of disease directed to the minor H antigens, and that initial indications were that highly purified preparations of these cells were capable of mediating GVHD, without apparent 'help' from mature donor-derived CD4+ T cells. To further strengthen this hypothesis, the current study was undertaken with the B10.BR----CBA strain combination in which irradiated recipient mice were additionally treated with an anti-CD4 monoclonal antibody, as a single or repeated injection, to minimize the presence of either residual host CD4+ cells or recently generated donor-derived CD4+ cells at later stages of disease development. The results indicate that these treatments do not affect the GVHD outcome and that the CD8+ cells are indeed capable of inducing disease independent of CD4+ 'help'. The addition of donor CD4+ T cells in the inoculum, however, does enhance the potential of these CD8+ cells, and is observed with both low and high dosages of CD4+ cells. CD4+ T cells, on their own, have also been observed to cause GVHD directed to minor H antigens in certain strain combinations, and their response has been further characterized in this study. Results indicate that CD4+ cells capable of mediating GVHD in the B10.D2----DBA/2 strain combination can do so over a wide range of recipient irradiation exposures. The transfer of high dosages of CD4+ cells only shortens survival times of the recipients and does not afford any apparent protection phenomenon as previously observed in CD4+ cell mediated anti-class II MHC GVHD. The study also indicates that neither CD4+ nor CD8+ cells responsible for GVHD directed to minor H antigens seem capable of targeting host stem cell elements.
Department of Microbiology and Immunology, Jefferson Cancer Institute, Jefferson Medical College, Philadelphia, PA 19107.
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Korngold
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016827:CD8 Antigens / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D007953:Leukemia, Radiation-Induced / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D015778:Minor Histocompatibility Antigens / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D015778:Minor Histocompatibility Antigens