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1: Science. 2006 Sep 29;313(5795):1972-5. Epub 2006 Aug 24.
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Comment in:
Reversal of the TCR stop signal by CTLA-4.

Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, Wei B, Hogg N, Garside P, Rudd CE.

Cell Signalling Section, Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.

The coreceptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is pivotal in regulating the threshold of signals during T cell activation, although the underlying mechanism is still not fully understood. Using in vitro migration assays and in vivo two-photon laser scanning microscopy, we showed that CTLA-4 increases T cell motility and overrides the T cell receptor (TCR)-induced stop signal required for stable conjugate formation between T cells and antigen-presenting cells. This event led to reduced contact periods between T cells and antigen-presenting cells that in turn decreased cytokine production and proliferation. These results suggest a fundamentally different model of reverse stop signaling, by which CTLA-4 modulates the threshold for T cell activation and protects against autoimmunity.

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PMID: 16931720 [PubMed - indexed for MEDLINE]