Critical role of CD4+CD25+ regulatory T cells in preventing murine autoantibody-mediated thrombocytopenia

Tetsuya Nishimoto, Takashi Satoh, Tsutomu Takeuchi, Yasuo Ikeda, Masataka Kuwana

研究成果: Article査読

37 被引用数 (Scopus)


Autoimmune response suppression by regulatory T cells (Tregs) helps to maintain peripheral immune tolerance, and defects in this mechanism are thought to play a role in the pathogenesis of various autoimmune diseases. In patients with immune thrombocytopenia, naturally occurring CD4+CD25+ Tregs are both functionally impaired and reduced in number. This study was undertaken to investigate Tregs' role in preventing immune thrombocytopenia in mice. Treg-deficient mice were prepared by inoculation of Treg-depleted CD4+CD25- T cells isolated from BALB/c mice into syngeneic nude mice intravenously. Platelet count, proportion of reticulated platelets, platelet-associated IgG, platelet-associated anti-platelet antibodies, and IgG anti-platelet antibody production in splenocyte cultures were examined by flow cytometry. Of 69 Treg-deficient mice, 25 (36%) spontaneously developed thrombocytopenia that lasted at least 5 weeks. The platelet-associated IgG level and proportion of reticulated platelets were elevated in the thrombocytopenic mice. Platelet eluates and splenocyte culture supernatants prepared from thrombocytopenic mice, but not from nonthrombocytopenic mice, contained IgG antibodies capable of binding to intact platelets. Simultaneous transfer of Tregs completely prevented the onset of thrombocytopenia, but Treg transfer after the onset of thrombocytopenia had no apparent effect. Treatment with IgG anti-cytotoxic T lymphocyte-associated antigen 4 antibody canceled this Treg-governed suppressive effect. In summary, these results indicate that Tregs play a critical role in preventing murine autoantibody-mediated thrombocytopenia by engaging cytotoxic T lymphocyte-associated antigen 4.

ジャーナルExperimental Hematology
出版ステータスPublished - 2012 4

ASJC Scopus subject areas

  • 分子生物学
  • 血液学
  • 遺伝学
  • 細胞生物学
  • 癌研究


「Critical role of CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells in preventing murine autoantibody-mediated thrombocytopenia」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。