CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with a complex pathogenesis, which includes both antibody- and T-cell-mediated effector mechanisms. Rituximab (an anti-human CD20 monoclonal antibody [mAb]) is one of the treatments for ITP and is known to deplete B cells but may also work by affecting the T-cell compartments. Here, we investigated the outcome of B-cell depletion (Bdep) therapy on CD8+ T-cell-mediated ITP using a murine model. CD6+ knockout (KO) mice were immunized withCD611 platelets, and T-cell-mediated ITP was initiated by transfer of their splenocytes into severe combined immunodeficiency (SCID) mice. The CD61 KO mice were administrated an anti-mouse CD20 mAb either before or after CD611 platelet immunization. This resulted in efficient Bdep in vivo, accompanied by significant increases in splenic and lymph node CD4+ and CD8+ T cells and proportional increases of FOXP3+ in CD4+and CD8+ T cells. Moreover, Bdep therapy resulted in significantly decreased splenic CD8+ T-cell proliferation in vitro that could be rescued by interleukin-2. This correlated with normalization of in vivo platelet counts in the transferred SCID mice suggesting that anti-CD20 therapy significantly reduces the ability of CD8+ T cells to activate and mediate ITP.