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Eur J Immunol. 1999 Dec;29(12):3887-97.

Modulation of TCR signaling by beta1 integrins: role of the tyrosine phosphatase SHP-1.

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INSERM U343 Hôpital de l'Archet, Nice, France.


When cross-linked, beta1 integrins co-activate T cells together with a TCR-CD3 signal. Soluble anti-beta1 monoclonal antibodies, however, inhibit T cell activation. We report inhibition of early tyrosine kinases, including ZAP-70, p59(fyn), CD4-associated p56(lck) and TCR components under this condition. The tyrosine phosphatase SHP-1 is activated by engagement of beta1 integrins and is implicated in this negative regulation since no inhibition occurs in SHP-1 dominant-negative T cells. As shown by the use of Lck-deficient cells, the activation of the protein tyrosine phosphatase depends on a pool of p56(lck) that is not associated with CD4. These cross-talk events were also observed with the alpha4beta1 integrin ligand, VCAM-1. We propose that these results may be important in terms of lymphocyte circulation; while T cells migrate through the vascular endothelium, they are primed for an amplified response; as inflammation develops, a local accumulation of soluble integrin ligands may help to turn it off.

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