Costimulation of CD28− T Cells Through CD3 and β1-Integrins Induces a Limited Th1 Cytokine Response

The costimulatory molecule CD28 regulates antigen-specific T-cell proliferation and the synthesis of multiple cytokines. The absence of CD28 on a subset of CD8bright+ T cells suggests that these cells may utilize alternative costimulatory pathways or have a limited cytokine response to presented antigen. We used fibronectin, a ligand for the beta1-integrins alpha4beta1 and alpha5beta1, as an alternate costimulatory ligand to assess the functional phenotype of CD8bright+CD28- T cells. CD25 expression was significantly up-regulated in CD8bright+CD28- T cells by immobilized anti-CD3i with fibronectin. Costimulation with fibronectin also significantly augmented anti-CD3i-induced IFN-gamma production only among CD8bright+CD28- T cells. The CD8bright+CD28- T cells did not produce significant IL-2 and IL-10 even in response to maximal stimulation with phorbol myristate acetate and ionomycin. These data support a costimulatory role for ss1-integrins in CD8bright+CD28- T cells and indicate that CD8bright+ CD28- T cells have a restricted Th1 cytokine repertoire.