4-1BB costimulation promotes human T cell adhesion to fibronectin

CD28 and 4-1BB (CD137) are costimulatory molecules for T cells. In this stu dy we investigated the role of 4-1BB in T cell adhesion to fibronectin (FN) . Unlike CD28, 4-1BB is present in only a small subset of T cells prepared from fresh human peripheral blood mononuclear cells, but was induced after prolonged TCR/CD28 activation in vitro. 4-1BB-expressing T cells were chara cteristically unique in their strong responsiveness to FN. Anti-4-1BB cross -linking synergized CD28 costimulation by lowering the threshold of CD3 sig nal required for CD28-mediated maximal proliferative response. In addition to increasing proliferative responses, 4-1BB promoted T cell adhesion to FN in the presence of CD28 costimulation. 4-1BB-mediated cell adhesion to FN was blocked by anti-beta 1 integrin, suggesting that 4-1BB mediates pi inte grin activation. The role of 4-1BB in inducing CD4(+) T cell adhesion to FN was confirmed by showing that the human leukemic CD4(+) T cell line, Jurka t, when transfected with cDNA encoding 4-1BB, became adherent to FN with an ti-4-1BB stimulation. Taken together, our results suggest that 4-1BB-promot ed T cell adhesion to extracellular matrix proteins is an important post ac tivation process for T cell migration, (C) 1999 Academic Press.