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

Li Guo, Rick Kapur, Rukshana Aslam, Edwin R. Speck, Anne Zufferey, Yajing Zhao, Michael Kim, Alan H. Lazarus, Heyu Ni and John W. Semple

Key points

  • CD20 B cell depletion therapy inhibits CD8+ T cell proliferation in vitro.

  • CD20 B cell depletion therapy prevents CD8+ T cell-mediated ITP in vivo.

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) 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. CD61 knockout (KO) mice were immunized with CD61+ platelets and T cell-mediated ITP was initiated by transfer of their splenocytes into severe combined immunodeficient (SCID) mice. The CD61 KO mice were administrated an anti-mouse CD20 monoclonal antibody either before or after CD61+ 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 (IL-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.

  • Submitted June 30, 2015.
  • Accepted November 8, 2015.