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Allogeneic platelet transfusions prevent murine T-cell-mediated immune thrombocytopenia

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Author

  • Li Guo
  • Lei Yang
  • Edwin R Speck
  • Rukhsana Aslam
  • Michael Kim
  • Christopher G J McKenzie
  • Alan H Lazarus
  • Heyu Ni
  • Ming Hou
  • John Freedman
  • John W Semple
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Summary, in English

Platelet transfusions are life-saving treatments for many patients with thrombocytopenia; however, their use is generally discouraged in the autoimmune disorder known as immune thrombocytopenia (ITP). We examined whether allogeneic platelet major histocompatibility complex (MHC) class I transfusions affected antiplatelet CD61-induced ITP. BALB/c CD61 knockout mice (CD61(-)/H-2(d)) were immunized against platelets from wild-type syngeneic BALB/c (CD61(+)/H-2(d)), allogeneic C57BL/6 (CD61(+)/H-2(b)), or C57BL/6 CD61 KO (CD61(-)/H-2(b)) mice, and their splenocytes were transferred into severe combined immunodeficient (SCID) mice to induce ITP. When nondepleted splenocytes were transferred to induce antibody-mediated ITP, both CD61(+) platelet immunizations generated immunity that caused thrombocytopenia independently of allogeneic MHC molecules. In contrast, when B-cell-depleted splenocytes were transferred to induce T-cell-mediated ITP, transfer of allogeneic MHC-immunized splenocytes completely prevented CD61-induced ITP development. In addition, allogeneic platelet transfusions into SCID mice with established CD61-induced ITP rescued the thrombocytopenia. Compared with thrombocytopenic mice, bone marrow histology in the rescued mice showed normalized megakaryocyte morphology, and in vitro CD61-specific T-cell cytotoxicity was significantly suppressed. These results indicate that antibody-mediated ITP is resistant to allogeneic platelet transfusions, while the T-cell-mediated form of the disease is susceptible, suggesting that transfusion therapy may be beneficial in antibody-negative ITP.

Publishing year

2014-01-16

Language

English

Pages

7-422

Publication/Series

Blood

Volume

123

Issue

3

Document type

Journal article

Publisher

American Society of Hematology

Keywords

  • Animals
  • Bone Marrow Cells
  • Disease Models, Animal
  • Female
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Integrin beta3
  • Megakaryocytes
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Platelet Transfusion
  • Spleen
  • T-Lymphocytes
  • Thrombocytopenia
  • Time Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't

Status

Published

ISBN/ISSN/Other

  • ISSN: 1528-0020