CTLA-4, an essential immune-checkpoint for T-Cell activation

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The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition. Subsequent studies by many researchers revealed the more complex mode of T-cell inhibition by CTLA-4. After T-cell activation, CTLA-4 is stored in the intracellular vesicles, and recruited to the immunological synapse formed between T cells and APCs, and inhibits further activation of T cells by blocking signals initiated by T-cell receptors and CD28. CTLA-4-positive cells can also provide cell-extrinsic regulation on other autoreactive T cells, and are considered to provide an essential regulatory mechanism for FoxP3+ regulatory T cells. Genetic deficiency of CTLA-4 leads to CD28-mediated severe autoimmunity in mice and humans, suggesting its function as a fundamental brake that restrains the expansion and activation of self-reactive T cells. In cancer, therapeutic approaches targeting CTLA-4 by humanized blocking antibodies has been demonstrated to be an effective immunotherapy by reversing T-cell tolerance against tumors. This chapter introduces CTLA-4 biology, including its discovery and mechanism of action, and discusses questions related to CTLA-4.

元の言語English
ホスト出版物のタイトルCurrent Topics in Microbiology and Immunology
出版者Springer Verlag
ページ99-126
ページ数28
410
DOI
出版物ステータスPublished - 2017 1 1

出版物シリーズ

名前Current Topics in Microbiology and Immunology
410
ISSN(印刷物)0070-217X
ISSN(電子版)2196-9965

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)

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  • これを引用

    Chikuma, S. (2017). CTLA-4, an essential immune-checkpoint for T-Cell activation. : Current Topics in Microbiology and Immunology (巻 410, pp. 99-126). (Current Topics in Microbiology and Immunology; 巻数 410). Springer Verlag. https://doi.org/10.1007/82_2017_61