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 beta 1 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- gamma delta TCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL-2 receptor) but not resting CD25low gamma delta T 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 alpha 4 subunit. Most FN binding is mediated by VLA-4. Additionally, resting gamma delta T cells cultured on coimmobilized anti-TCR delta 1 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 gamma delta T cells cultured on immobilized anti-TCR delta 1 mAb alone. Also expression of CD25 was significantly enhanced on cells cultured on coimmobilized anti-TCR delta 1 mAb and FN, indicative of T cell activation. Cross-linking of VLA-4 and VLA-5 molecules costimulated expansion of resting gamma delta T cells induced by cross-linked TCR delta 1. These results suggest that the gamma delta T cell beta 1 integrins, VLA-4 and VLA-5, may function in a dual capacity as signalling and adhesion molecules.
Laboratory of Immunology, Sansum Medical Research Foundation, Santa Barbara, CA 93105.
M
M
Avdalovic
D
D
Fong
B
B
Formby
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002455:Cell Division; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D017469:Receptors, Fibronectin / Q000187:drug effects / Q000276:immunology*; D015375:Receptors, Interleukin-2; D016029:Receptors, Very Late Antigen / Q000187:drug effects / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D009842:Oligopeptides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017469:Receptors, Fibronectin; D015375:Receptors, Interleukin-2; D016029:Receptors, Very Late Antigen; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline