ACUTE GRAFT-VERSUS-HOST DISEASE WITHOUT COSTIMULATION VIA CD28

T lymphocyte activity is enhanced by costimulatory signals mediated th rough CD28 binding to B7-1/B7-2 on antigen-presenting cells. Several r ecent studies have shown that graft-versus-host disease (GVHD) can be inhibited by in vivo treatment with CTLA4Ig, which blocks CD28-B7 inte ractions. These findings prompted us to investigate the role of CD28 i n acute GVHD, using gene-targeted mice. We performed the experiments i n the context of strong allogeneic MHC stimulation (H2(b) anti-H2(d)) and weak stimulation (H2(d) anti-H2(b)). In both directions, efficient in vitro T-cell cytotoxicity and acute lethal GVHD were induced by CD 28-deficient lymphocytes, which was only partially delayed when compar ed with wild-type mice. We conclude that lethal GVHD can develop witho ut costimulation via CD28.