Format

Send to

Choose Destination
Trends Immunol. 2015 Feb;36(2):63-70. doi: 10.1016/j.it.2014.12.001. Epub 2015 Jan 9.

Confusing signals: recent progress in CTLA-4 biology.

Author information

1
Institute for Immunity & Transplantation, University College London Division of Infection & Immunity, Royal Free Campus, London, NW3 2PF, UK. Electronic address: lucy.walker@ucl.ac.uk.
2
Institute for Immunity & Transplantation, University College London Division of Infection & Immunity, Royal Free Campus, London, NW3 2PF, UK. Electronic address: d.sansom@ucl.ac.uk.

Abstract

The mechanism of action of cytotoxic T-lymphocyte-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.

KEYWORDS:

CD28; CTLA-4; T cell activation; T cell tolerance; costimulation

PMID:
25582039
PMCID:
PMC4323153
DOI:
10.1016/j.it.2014.12.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center