Title |
CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell–mediated immune thrombocytopenia
|
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Published in |
Blood, November 2015
|
DOI | 10.1182/blood-2015-06-655126 |
Pubmed ID | |
Authors |
Li Guo, Rick Kapur, Rukshana Aslam, Edwin R Speck, Anne Zufferey, Yajing Zhao, Michael Kim, Alan H Lazarus, Heyu Ni, John W Semple |
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. |
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Unknown | 2 | 40% |
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Science communicators (journalists, bloggers, editors) | 2 | 40% |
Mendeley readers
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Other | 5 | 11% |
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