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

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Author

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

Summary, in English

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.

Publishing year

2016-02-11

Language

English

Pages

8-735

Publication/Series

Blood

Volume

127

Issue

6

Document type

Journal article

Publisher

American Society of Hematology

Keywords

  • Animals
  • Antigens, CD20
  • B-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Integrin beta3
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Platelet Count
  • Purpura, Thrombocytopenic, Idiopathic
  • Journal Article
  • Research Support, Non-U.S. Gov't

Status

Published

ISBN/ISSN/Other

  • ISSN: 1528-0020