Costimulation of CD28(-) T cells through CD3 and beta(1)-integrins inducesa limited Th1 cytokine response

The costimulatory molecule CD28 regulates antigen-specific T-cell prolifera tion and the synthesis of multiple cytokines. The absence of CD28 on a subs et of CD8(bright+) T cells suggests that these cells may utilize alternativ e costimulatory pathways or have a limited cytokine response to presented a ntigen. We used fibronectin, a ligand for the beta(1)-integrins alpha(4)bet a(1), and alpha(5)beta(1), as an alternate costimulatory ligand to assess t he functional phenotype of CD8(bright+)CD28(-) T cells. CD25 expression was significantly up-regulated in CD8(bright+)CD28(-) T cells by immobilized a nti-CD3(i) with fibronectin, Costimulation with fibronectin also significan tly augmented anti-CD3(i)-induced IFN-gamma production only among CD8(brigh t+)CD28(-) T cells, The CD8(bright+)CD28(-) T cells did not produce signifi cant IL-2 and IL-10 even in response to maximal stimulation with phorbol my ristate acetate and ionomycin, These data support a costimulatory role for beta(1)-integrins in CD8(bright+)CD28(-) T cells and indicate that CD8(brig ht+)CD28(-) T cells have a restricted Th1 cytokine repertoire.