Integrin alpha 4 beta 7 co-stimulation of human peripheral blood T cell proliferation.
The integrin alpha 4 beta 7 mediates lymphocytes adhesion to VCAM-1 on activated endothelium, fibronectin in the extracellular matrix, and the mucosal vascular addressin MAdCAM-1. It is unclear whether alpha 4 beta 7 performs any function beyond directing specific adhesion reactions. We addressed the possibility that triggering of alpha 4 beta 7 with a specific monoclonal antibody was capable of delivering an accessory stimulus that would coactivate T cells and lead to proliferation. At submitogenic levels of anti-CD3 stimulation, triggering of alpha 4 beta 7 by immobilized mAb ACT-1 resulted in T cell blastogenesis, IL-2 production, expression of the IL-2 receptor alpha chain CD25, and ultimately DNA synthesis. These results indicate that the integrin alpha 4 beta 7 is involved in more than lymphocyte adhesion and homing but also plays a role in cell signaling.
Teague
T K
TK
Department of Immunology, University of Texas M. D. Anderson Cancer, Center, Houston 77030, USA.
Lazarovits
A I
AI
McIntyre
B W
BW
D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016023:Integrins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; C071777:integrin alpha4beta7