ACTIVATED T-CELL ADHESION TO THROMBOSPONDIN IS MEDIATED BY THE ALPHA-4-BETA-1 (VLA-4) AND ALPHA-5-BETA-1 (VLA-5) INTEGRINS

T lymphocytes utilize adhesion receptors in a regulated manner to inte ract with other cells and with components of the extracellular matrix. These cell-cell and cell-matrix interactions serve a critical role in T cell recognition of foreign Ag and in the migration of T cells to v arious anatomic sites in vivo. Thrombospondin is an extracellular matr ix protein that is transiently expressed at high concentration in dama ged and inflamed tissue. Given recent evidence implicating a role for the extracellular matrix in modulating T-cell migration and function, we analyzed T-lymphocyte interactions with thrombospondin. We show her e that CD4+ T cells specifically adhere to thrombospondin predominantl y via the 70 kDa core region of the thrombospondin molecule. Antibody blocking and affinity chromatography analysis suggest that T-cell adhe sion to thrombospondin involves three distinct receptors: an activatio n-independent receptor that mediates adhesion of resting T cells, and the alpha4beta1 and alpha5beta1 integrins, which mediate a rapid incre ase in adhesion to thrombospondin upon activation. These three molecul es appear to be novel thrombospondin receptors, as other receptors pre viously implicated in the adhesion of non-lymphoid cells to thrombospo ndin appear not to be involved in T-cell/thrombospondin interactions. The up-regulation of alpha4beta1 and alpha5beta1 functional activity u pon activation is associated with the preferential adhesion of memory T cells to thrombospondin. Our results thus define three novel thrombo spondin receptors, and provide additional evidence that extracellular matrix proteins play an important role in lymphocyte migration into, a nd retention in, inflammatory sites,