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

Authors:
John W Semple
John W Semple
Lund University
Professor of Transfusion Medicine
Lund, Skane | Sweden

Blood 2016 Feb 10;127(6):735-8. Epub 2015 Nov 10.

The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and Department of Medicine, Department of Laboratory Medicine and Pathobiology, and Department of Pharmacology, University of Toronto, Toronto, ON, Canada.

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.

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http://www.bloodjournal.org/content/bloodjournal/127/6/735.f
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http://www.bloodjournal.org/cgi/doi/10.1182/blood-2015-06-65
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February 2016
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