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

Research output: Chapter in Book/Report/Conference proceedingChapter

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Title of host publicationCurrent Topics in Microbiology and Immunology
PublisherSpringer Verlag
Pages99-126
Number of pages28
Volume410
DOIs
Publication statusPublished - 2017 Jan 1

Publication series

NameCurrent Topics in Microbiology and Immunology
Volume410
ISSN (Print)0070-217X
ISSN (Electronic)2196-9965

Fingerprint

T-Lymphocytes
Antigen-Presenting Cells
CD86 Antigens
Immunological Synapses
Antibodies, Monoclonal, Humanized
Blocking Antibodies
Viral Tumor Antigens
Regulatory T-Lymphocytes
T-Cell Antigen Receptor
Autoimmunity
Immunotherapy
Neoplasms
Research Personnel
Ligands

ASJC Scopus subject areas

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

Cite this

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

CTLA-4, an essential immune-checkpoint for T-Cell activation. / Chikuma, Shunsuke.

Current Topics in Microbiology and Immunology. Vol. 410 Springer Verlag, 2017. p. 99-126 (Current Topics in Microbiology and Immunology; Vol. 410).

Research output: Chapter in Book/Report/Conference proceedingChapter

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