期刊
TRENDS IN IMMUNOLOGY
卷 36, 期 2, 页码 63-70出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.it.2014.12.001
关键词
CTLA-4; CD28; costimulation; T cell tolerance; T cell activation
类别
资金
- Medical Research Council Senior Fellowship
- Biotechnology and Biological Sciences Research Council [BB/H013598/2] Funding Source: researchfish
- Diabetes UK [12/0004477] Funding Source: researchfish
- Medical Research Council [G0802382] Funding Source: researchfish
- BBSRC [BB/H013598/2] Funding Source: UKRI
- MRC [G0802382] Funding Source: UKRI
The mechanism of action of cytotoxic T-Iymphocyte-associated protein 4 (CTLA-4) remains surprisingly unclear. Regulatory T (Treg) cells can use CTLA-4 to elicit suppression; however, CTLA-4 also operates in conventional T cells, reputedly by triggering inhibitory signals. Recently, interactions mediated via the CTLA-4 cytoplasmic domain have been shown to preferentially affect Treg cells, yet other evidence suggests that the extracellular domain of CTLA-4 is sufficient to elicit suppression. Here, we discuss these paradoxical findings in the context of CTLA-4-mediated ligand regulation. We propose that the function of CTLA-4 cytoplasmic domain is not to transmit inhibitory signals but to precisely control the turnover, cellular location, and membrane delivery of CTLA-4 to facilitate its central function: regulating the access of CD28 to their shared ligands.
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