Reversal of the TCR stop signal by CTLA-4

H Schneider, J Downey, A Smith, BH Zinselmeyer… - science, 2006 - science.org
H Schneider, J Downey, A Smith, BH Zinselmeyer, C Rush, JM Brewer, B Wei, N Hogg…
science, 2006science.org
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 …
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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