Journal
SCIENCE
Volume 313, Issue 5795, Pages 1972-1975Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1131078
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Funding
- Wellcome Trust Funding Source: Medline
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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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