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T-Cell Abnormalities

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Autoimmune Thrombocytopenia

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Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and reduced platelet production caused primarily by IgG antiplatelet autoantibodies, which mainly target platelet membrane glycoproteins (GPs), including GPIIb/IIIa and GPIb/IX. GPIIb/IIIa-reactive CD4+ T cells play a central role in the pathogenic process by triggering and maintaining antiplatelet autoantibodies. The mechanism for ongoing antiplatelet antibody production is explained by a “pathogenic loop” model consisting of macrophages in the reticuloendothelial system, GPIIb/IIIa-reactive CD4+ T cells, and B cells producing antiplatelet antibodies. Among T helper (Th) cell subsets, Th1 and Th17 cells as well as newly identified T follicular helper (Tfh) cells, which support B cell maturation and differentiation within the germinal center, are actively involved in antiplatelet antibody production. Finally, platelet-reactive CD8+ cytotoxic T cells directly induce lysis and apoptosis of circulating platelets as well as megakaryocytes. On the other hand, CD4+ regulatory T cells (Tregs), which contribute to maintenance of peripheral immune tolerance, are defective in patients with ITP, through decreased numbers and impaired function of Tregs. In fact, mice lacking Foxp3 Tregs spontaneously develop chronic thrombocytopenia mediated through the production of IgG antiplatelet autoantibodies. Further studies evaluating mechanisms for T-cell dysregulation are useful in elucidating the pathogenesis of ITP and in developing novel treatment strategies.

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Acknowledgments

We dedicate this chapter to the late Tetsuya Nishimoto, who had contributed to elucidation of autoimmune mechanisms of ITP.

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Authors and Affiliations

  1. Division of Hematology, Kitasato University School of Allied Health Sciences, 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0373, Japan

    Takashi Satoh

  2. Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan

    Takashi Satoh

  3. Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan

    Masataka Kuwana

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  1. Takashi Satoh
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  2. Masataka Kuwana
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Correspondence to Takashi Satoh .

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Editors and Affiliations

  1. Division of Hematology and Oncology Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Iwate, Japan

    Yoji Ishida

  2. Department of Blood Transfusion, Osaka University Hospital, Suita, Osaka, Japan

    Yoshiaki Tomiyama

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© 2017 Springer Nature Singapore Pte Ltd.

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Satoh, T., Kuwana, M. (2017). T-Cell Abnormalities. In: Ishida, Y., Tomiyama, Y. (eds) Autoimmune Thrombocytopenia　. Springer, Singapore. https://doi.org/10.1007/978-981-10-4142-6_6

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  • DOI: https://doi.org/10.1007/978-981-10-4142-6_6

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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-4141-9

  • Online ISBN: 978-981-10-4142-6

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