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.