CONCURRENT MCMV INFECTION AUGMENTS DONOR ANTIHOST-SPECIFIC ACTIVITY AND ALTERS CLINICAL OUTCOME FOLLOWING EXPERIMENTAL ALLOGENEIC BONE-MARROW TRANSPLANTATION

The present studies were undertaken to examine whether concurrent MCMV infection during allogeneic bone marrow transplantation (BMT) could a lter the developing donor-host immune interactions and affect the over all outcome of the transplant. In order to determine the effect of MCM V on antihost activity arising following an allogeneic BMT, specific d onor 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-M HC transplantation loci, augmented antihost cytotoxic activity mediate d by CD8+ T cells assayed directly from the recipient's spleen 10-14 d ays posttransplant. Notably, allogeneic BMT recipients receiving eithe r lethal or nonlethal numbers of donor T cells and inoculated with MCM V exhibited more rapid and profound weight loss compared with uninfect ed allogeneic and syngeneic BMT recipients. Concurrent virus presence also resulted in a markedly increased incidence of mortality in alloge neic 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-antire cipient-i.e., graft vs, host-reactivity. In total, the results support the notion that pathogens could complicate allogeneic BMT by contribu ting to the development of graft vs. host disease.