1. CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia.
- Author
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Li Guo, Kapur, Rick, Aslam, Rukshana, Speck, Edwin R., Zufferey, Anne, Yajing Zhao, Kim, Michael, Lazarus, Alan H., Heyu Ni, and Semple, John W.
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THROMBOCYTOPENIA treatment , *B cells , *CD20 antigen , *CD8 antigen , *RITUXIMAB , *LABORATORY mice , *PHYSIOLOGY - 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. CD61 knockout (KO) mice were immunized with CD61+ 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 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. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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