COMITOGENIC EFFECTS OF VERY LATE ACTIVATION ANTIGENS ON CD3-STIMULATED HUMAN THYMOCYTES - INVOLVEMENT OF VARIOUS TYROSINE KINASE PATHWAYS

Thymocytes display several integrins that are involved in cell-extrace llular matrix interactions and differentiation processes. We have exam ined the role of very late activation Ag (VLA) on human thymocyte stim ulation. VLA-4, VLA-5, and VLA-6 activated with either mAbs or their n atural ligands (fibronectin, laminin, and vascular cell adhesion molec ule-1) are able to transduce costimulatory signals in thymocytes activ ated via the CD3 pathway, i.e., enhancement of thymocyte proliferation , CD25 and CD69 expression, and IL-2 secretion. In contrast, activatio n of thymocytes with a mitogenic pair of CD2 mAb was not modified by V LA molecules. Cross-linking of both beta(1)- and alpha(5)-chains induc ed tyrosine phosphorylation of several proteins, whereas the cross-lin king of the alpha(4)- and alpha(6)-chains did not. Moreover, a differe nt pattern of tyrosine phosphorylation was observed when thymocytes we re activated via either beta(1)- or alpha(5)-chains. These results sug gest that VLA molecules activate tyrosine kinase pathways in thymocyte s, and that different pathways would be implicated during thymocyte in teractions with extracellular matrix or accessory cells, wh ich are li kely to play a role in thymocyte differentiation.