CD28/CTLA-4 and CD80/CD86 costimulatory molecules are mainly involved in acceptance or rejection of human liver transplant

CD28/CTLA-4 interaction wit their specific B7-ligands (CD80 and CD86) have decisive roles in antigenic and allogenic responses. Recently, experimental transplant studies demonstrated that donor-specific tolerance is achieved by blocking these interactions. The present study analyzes the expression o f these co-stimulatory molecules in peripheral blood cells from 74 liver re cipients and in 16 liver biopsies, which were classified into acute-rejecti on (AR, n = 27) and nonacute-rejection (NAR, n = 47) groups. as well as the ir influence on the in vitro response of in vivo allosensitized cells. The results clearly indicate that in human liver transplant too, B7 and CD28/CT LA-4 expression on B and CD4(+) peripheral lymphocytes respectively, contri butes to graft acceptance or rejection, and appears to be of crucial import ance in modulating the host alloresponse and specific-CTL generation. In th e NAR-group, costimulatory molecule expression remained at basal levels aft er transplant, whereas in the AR-group these molecules were significantly u pregulated on days of AR. CTLA-4 was observed in the infiltrating lymphocyt es in most of the biopsies, but CD80 or CD86 were not. Moreover, specific c ytotoxicity from the in vivo primed cells was clearly suppressed in the NAR -patients with low co-stimulatory molecule expression, whereas this activit y was not modified but rather stimulated in the AR-group. Together, these f indings indicate that intervention of CD28/CTLA-4/B7 signaling could be the rapeutically useful in clinical transplantation. Human Immunology 61, 658-6 69 (2000). (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.