Concurrent MCMV infection augments donor antihost-specific activity and alters clinical outcome following experimental allogenic bone marrow transplantation.

Abstract

The present studies were undertaken to examine whether concurrent MCMV infection during allogeneic bone marrow transplantation (BMT) could alter the developing donor-host immune interactions and affect the overall outcome of the transplant. In order to determine the effect of MCMV on antihost activity arising following an allogeneic BMT, specific donor antihost cytotoxicity was examined. The results demonstrated that concurrent virus infection in mice receiving a BMT from donors either H2-matched and non-MHC-mismatched or mismatched at both MHC and non-MHC transplantation loci, augmented antihost cytotoxic activity mediated by CD8+ T cells assayed directly from the recipient's spleen 10-14 days posttransplant. Notably, allogenic BMT recipients receiving either lethal or nonlethal numbers of donor T cells and inoculated with MCMV exhibited more rapid and profound weight loss compared with uninfected allogeneic and syngeneic BMT recipients. Concurrent virus presence also resulted in a markedly increased incidence of mortality in allogeneic BMT recipients of nonlethal numbers of T cells. We conclude from these findings that when virus is present early after allogeneic BMT, the resulting interactions can potentiate T cell-mediated donor-antirecipient--i.e., graft vs. host-reactivity. In total, the results support the notion that pathogens could complicate allogeneic BMT by contributing to the development of graft vs. host disease.