IN-VIVO CD40-GP39 INTERACTIONS ARE ESSENTIAL FOR THYMUS-DEPENDENT HUMORAL IMMUNITY .2. PROLONGED SUPPRESSION OF THE HUMORAL IMMUNE-RESPONSEBY AN ANTIBODY TO THE LIGAND FOR CD40, GP39

The ligand for CD40 has been recently identified as a 39-kd protein, g p39, expressed on the surface of activated CD4+ T helper cells (Th). I n vitro, soluble CD40 and anti-gp39 have been shown to block the abili ty of Th to activate B cells, suggesting that gp39-CD40 interactions a re important to T cell-dependent B cell activation. Here it is shown t hat in vivo administration of anti-gp39 dramatically reduced both prim ary and secondary humoral immune responses to erythrocytes and soluble protein antigens without altering responses to the T-independent type 11 antigen, trinitrophenyl-Ficoll. Treatment of mice for 4 d with ant i-gp39 inhibited the anti-sheep red blood cell (SRBC) response for at least 3 wk and inhibited the expression of all immunoglobulin isotypes in secondary responses to the protein antigen, keyhole limpet hemocya nin. To examine the direct effect of anti-gp39 on Th function, SRBC-im mune Th cells from anti-gp39-treated mice were adoptively transferred and shown to be fully capable of providing help. These results suggest that anti-gp39 treatment does not cause Th deletion or anergy. Anti-g p39 may mediate its profound immunosuppressive effects on humoral immu nity by blocking gp39-CD40 interactions. Moreover, these studies estab lish gp39-CD40 as an important receptor-ligand pair for the targeting of therapeutic antibodies to control thymus-dependent humoral response s.