INTERACTION OF CD31 WITH A HETEROPHILIC COUNTERRECEPTOR INVOLVED IN DOWN-REGULATION OF HUMAN T-CELL RESPONSES

CD31 is a 130-kD glycoprotein of the immunoglobulin (Ig) superfamily e xpressed on the surface of endothelial cells, platelets, and several l eukocyte subsets. Previous reports indicated that CD31 can mediate int ercellular adhesion via both homophilic and heterophilic interaction m echanisms. Using a soluble recombinant CD31-Ig fusion protein (CD33 re ceptor globulin [Rg]), we demonstrate here that human CD31(-) T lympho cytes and CD4(+)CD31(-) T cell clones express a heterophilic CD31 liga nd that is upregulated 18 h after activation. interaction of CD31Rg wi th CD31(-) T helper cell (Th) clones was divalent cation independent b ut could be blocked by heparin, thus indicating that the CD31 counterr eceptor on T cells can be distinguished from the ligands identified on other cell types. Moreover, a single chain protein of 120 kD was prec ipitated by CD31Rg from the lysates of CD31(-) Th clones. CD31Rg compl etely downregulated the proliferative response and cytokine production (interleukin-4, interferon-gamma, and tumor necrosis factor-alpha) of CD31(-) Th clones when the cells were maximally stimulated via immobi lized CD3 monoclonal antibody. These results suggest that interaction of CD31 with a heterophilic counterreceptor on T lymphocytes can inter fere with a positive regulatory pathway of T cell activation, or direc tly signal T cells to downregulate immune function.