VIRUS-ASSOCIATED IMMUNE-RESPONSES IN MICE UNDERGOING GVHR EXACERBATED BY CONCURRENT MCMV INFECTION

It has been proposed that virus-induced immune responses early postinjection of donor cells can result in the exacerbation of GVH reactions. Previously, we and others have shown that introduction of MCMV together with class I-disparate donor cells results in the development of severe GVH reactions. The present studies were performed to examine the nature of the immune responses induced by concurrent MCMV infection early during GVHR. Within 3 days and continuing through day 10 postinjection, spleens from recipients of virus + GVHR inocula exhibited enhanced cytotoxic activity against YAC-1 target cells effected by a Thy1-Lyt2-ASGM1+NK1.1+ population. Notably, within one week after virus and GVHR injection, sera from those animals were found to contain specific anti-MCMV IgM antibody at levels comparable to those induced in mice injected only with virus. However, in contrast to recipients of MCMV alone, sera from virus + GVHR animals never contained anti-MCMV IgG antibody. To determine the effect of virus on a discrete donor antihost response, antihost cytotoxic activity was examined. By 7 days postinjection, the spleens of virus + GVHR but not GVHR-only recipients contained marked levels of specific antihost cytotoxic activity, mediated by a Thy1+Lyt-2+ASGM1+NK1.1- population. In total, these findings support the hypothesis that early virus-induced immune responses may promote the development of severe graft-versus-host responses including the enhancement of donor antihost specific cytotoxic T cells.