INDUCTION OF UNRESPONSIVENESS TO HEYMANN NEPHRITIS - INHIBITED BY MONOCLONAL-ANTIBODY TO CD4 BUT NOT TO CD8

The effects of mAb therapy to CD4 or CD8 on induction of unresponsiveness to Heymann's nephritis by preimmunization with renal tubular antigen in IFA. Anti-CD4 mAbs (MRC Ox35) given for 2 weeks after RTA/IFA completely prevented the induction of resistance to HN, all rats developing proteinuria as well as high titers of autoantibody and Ig and C deposits in glomeruli. Anti-CD8 mAbs (MRC Ox8) did not prevent induction of unresponsiveness, even though it totally depleted CD8+ cells. In control rats not preimmunized with RTA/IFA, mAb therapy did not suppress disease induction, but in the case of anti-CD4 therapy enhanced the severity of disease. Persistent depletion of T cell subsets or complement components did not explain the effects of mAb therapy. These studies suggest that CD4+ cells are critical for the induction of unresponsiveness to HN and that therapy with mAb to CD4 can prevent induction of tolerance to an antigen, which has implications for its use in the induction of tolerance. © 1991.