CD8+ and CD4+ T cells contribute to the exacerbation of class I MHC disparate graft-vs-host reaction by concurrent murine cytomegalovirus infection.
Concurrent infection with MCMV has been observed to result in the marked exacerbation of a P-->F1 GVHR across a class I MHC only donor-recipient disparity. We have previously determined that MCMV induces several alterations characteristic of severe GvHR/D which are not observed during GvHR or MCMV infection alone. Most notable of these alterations is the enhanced development of donor anti-host cytotoxic T cell activity. The present studies were performed to examine the requirement of specific donor and host cell populations. Only depletion of donor CD8+ T cells (not NK1.1+ or CD4+) prevented development of severe GVHR/D. By in vivo antibody treatments, depletion of host CD4+ but not CD8+ T cells also abrogated the development of severe GVHR/D. These findings therefore support the hypothesis that MCMV-activated CD4+ T cells enhance the production of a donor anti-host class I CD8+ response. Thus, the present findings support hypotheses attributing the association of viral infection and GVHD development with pathogen-induced immune responses.
Cray
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Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101.
Levy
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RB
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D016827:CD8 Antigens / Q000032:analysis*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006087:Graft vs Host Reaction / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I