Chapter title |
CTLA-4, an Essential Immune-Checkpoint for T-Cell Activation
|
---|---|
Chapter number | 61 |
Book title |
Emerging Concepts Targeting Immune Checkpoints in Cancer and Autoimmunity
|
Published in |
Current topics in microbiology and immunology, January 2017
|
DOI | 10.1007/82_2017_61 |
Pubmed ID | |
Book ISBNs |
978-3-31-968928-9, 978-3-31-968929-6
|
Authors |
Shunsuke Chikuma |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 109 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 16 | 15% |
Student > Ph. D. Student | 15 | 14% |
Student > Master | 14 | 13% |
Researcher | 9 | 8% |
Student > Doctoral Student | 5 | 5% |
Other | 8 | 7% |
Unknown | 42 | 39% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 24 | 22% |
Immunology and Microbiology | 14 | 13% |
Medicine and Dentistry | 10 | 9% |
Agricultural and Biological Sciences | 7 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 2% |
Other | 6 | 6% |
Unknown | 46 | 42% |