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

• Published in: European journal of immunology 1999-12, Vol.29 (12), p.3887-3897
• Main Authors: Mary, F, Moon, C, Venaille, T, Thomas, M L, Mary, D, Bernard, A
• Format: Article
• Language: English
• Subjects: vascular endothelium
• ISSN: 0014-2980
• DOI: 10.1002/(SICI)1521-4141(199912)29:12<3887::AID-IMMU3887>3.0.CO;2-A

When cross-linked, beta 1 integrins co-activate T cells together with a TCR-CD3 signal. Soluble anti- beta 1 monoclonal antibodies, however, inhibit T cell activation. We report inhibition of early tyrosine kinases, including ZAP-70, p59 super(fyn), CD4-associated p56 super(lck) and TCR components under this condition. The tyrosine phosphatase SHP-1 is activated by engagement of beta 1 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 super(lck) that is not associated with CD4. These cross-talk events were also observed with the alpha 4 beta 1 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.