ADHESION AND COSTIMULATION OF PROLIFERATIVE RESPONSES OF HUMAN GAMMA-DELTA T-CELLS BY INTERACTION OF VLA-4 AND VLA-5 WITH FIBRONECTIN

The very late antigens, VLA-4 and VLA-5 belong to the beta1 subfamily of integrins and have been identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3 and VLA-6 expressed on human CD3+CD4-CD8- gammadeltaTCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL-2 receptor) but not resting CD25low gammadeltaT cells specifically adhere to FN. The binding capacity is inhibited by the synthetic peptide GRGDSP which inhibits adhesion mediated by VLA-5 and a functional mAb directed against the alpha4 subunit. Most FN binding is mediated by VLA-4. Additionally, resting gammadelta T cells cultured on coimmobilized anti-TCRdelta1 mAb and FN or the 40 kDa fragment (which contains the adhesion site in the IIICS domain recognized by VLA-4) for 96 h in the absence of exogeneous IL-2 showed significant increase in proliferation when compared to that of resting gammadelta T cells cultured on immobilized anti-TCRdelta1 mAb alone. Also expression of CD25 was significantly enhanced on cells cultured on coimmobilized anti-TCRdelta1 mAb and FN, indicative of T cell activation. Cross-linking of VLA-4 and VLA-5 molecules costimulated expansion of resting gammadelta T cells induced by cross-linked TCRdelta1. These results suggest that the gammadelta T cell beta1 integrins, VLA-4 and VLA-5, may function in a dual capacity as signalling and adhesion molecules.