IDENTIFICATION OF A NOVEL INDUCIBLE CELL-SURFACE LIGAND OF CD5 ON ACTIVATED LYMPHOCYTES

CD5 is a 67-kD glycoprotein that is expressed on most T lymphocytes an d on a subset of mature B cells. Although its physiologic function is unknown, several lines of evidence suggest that CD5 may play a role in the regulation of T cell activation and in T cell-antigen presenting cell interactions. Using a CD5-immunoglobulin fusion protein (CD5Rg, f or receptorglobulin), we have uncovered a new CD5 ligand (CD5L) expres sed on the surface of activated splenocytes. Stimulation of murine spl enocytes with anti-CD3 and anti-CD28 antibodies induces transient expr ession of CD5L on B lymphocytes that lasts for similar to 72 h. Bindin g of CD5Rg to activated splenocytes is trypsin-resistant and independe nt of divalent cations. However, it is pronase sensitive and dependent on N-linked glycosylation of CD5, since treatment of CD5Rg with PNGas eF or N-glycanase completely abrogates its ability to bind activated s plenocytes. In addition to splenocytes, CD5L is expressed on activated murine T cell clones. Immunoprecipitation, antibody, and recombinant protein blocking studies indicate that CD5L is distinct from CD72, whi ch has been proposed to be a CD5 ligand. To determine whether CD5-CD5L interaction might play a role in vivo, we tested the effect of CD5Rg in a murine model of antibody-mediated membranous glomerulonephritis. Injection of CD5Rg was found to abrogate development of the disease. T aken together, our results help identify a novel ligand of CD5 and pro pose a role for CD5 in the regulation of immune responses.