Reversal of the TCR stop signal by CTLA-4

J.M. Brewer, Helga Schneider, Jos Downey, Andrew Smith, B.H. Zinselmeyer, Catherine Rush

Research output: Contribution to journalArticle

398 Citations (Scopus)

Abstract

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.
LanguageEnglish
Pages1972-1975
Number of pages3
JournalScience
Volume313
Issue number5795
DOIs
Publication statusPublished - 2006

Fingerprint

CTLA-4 Antigen
T-Cell Antigen Receptor
T-Lymphocytes
Viral Tumor Antigens
Antigen-Presenting Cells
Autoimmunity
Photons
Confocal Microscopy
Cell Movement
Cytokines

Keywords

  • biophotonics
  • cells
  • microscopy
  • lasers
  • t cells

Cite this

Brewer, J. M., Schneider, H., Downey, J., Smith, A., Zinselmeyer, B. H., & Rush, C. (2006). Reversal of the TCR stop signal by CTLA-4. Science, 313(5795), 1972-1975. https://doi.org/10.1126/science.1131078
Brewer, J.M. ; Schneider, Helga ; Downey, Jos ; Smith, Andrew ; Zinselmeyer, B.H. ; Rush, Catherine. / Reversal of the TCR stop signal by CTLA-4. In: Science. 2006 ; Vol. 313, No. 5795. pp. 1972-1975.
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Brewer, JM, Schneider, H, Downey, J, Smith, A, Zinselmeyer, BH & Rush, C 2006, 'Reversal of the TCR stop signal by CTLA-4' Science, vol. 313, no. 5795, pp. 1972-1975. https://doi.org/10.1126/science.1131078

Reversal of the TCR stop signal by CTLA-4. / Brewer, J.M.; Schneider, Helga; Downey, Jos; Smith, Andrew; Zinselmeyer, B.H.; Rush, Catherine.

In: Science, Vol. 313, No. 5795, 2006, p. 1972-1975.

Research output: Contribution to journalArticle

TY - JOUR

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AB - 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.

KW - biophotonics

KW - cells

KW - microscopy

KW - lasers

KW - t cells

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Brewer JM, Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C. Reversal of the TCR stop signal by CTLA-4. Science. 2006;313(5795):1972-1975. https://doi.org/10.1126/science.1131078