Interaction o f CD 31 with a Heterophil ic Counterreceptor Involved in Downregulat ion o f H u m a n T Cell

CD31 is a 130-kD glycoprotein of the immunoglobulin (Ig) superfamily expressed on the surrice of endothelial cells, platelets, and several leukocyte subsets. Previous reports indicated that CD31 can mediate intercellular adhesion via both homophilic and heterophilic interaction mechanisms. Using a soluble recombinant CD31-Ig fusion protein (CD31 receptor globulin [Rg]), we demonstrate here that human CD31T lymphocytes and CD4+CD31T cell clones express a heterophilic CD31 ligand that is upregulated 18 h after activation. Interaction of CD31Kg with CD31T helper cell (Th) clones was divalent cation independent but could be blocked by heparin, thus indicating that the CD31 counterreceptor on T cells can be distinguished from the ligands identified on other cell types. Moreover, a single chain protein of 120 kD was precipitated by CD31Rg from the lysates of CD31Th clones. CD31Rg completely downregulated the proliferative response and cytokine production (interleukin-4, interferon-% and tumor necrosis factor-o 0 of CD31Th clones when the cells were maximally stimulated via immobilized CD3 monoclonal antibody. These results suggest that interaction of CD31 with a heterophilic counterreceptor on T lymphocytes can interfere with a positive regulatory pathway of T cell activation, or directly signal T cells to downregulate immune function.