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 CD8(bright+) 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 β1-integrins α4β1 and α5β1, as an alternate costimulatory ligand to assess the functional phenotype of CD8(bright+)CD28- T cells. CD25 expression was significantly up-regulated in CD8(bright+)CD28- T cells by immobilized anti- CD3(i) with fibronectin. Costimulation with fibronectin also significantly augmented anti-CD3(i)-induced IFN-γ production only among CD8(bright+)CD28- T cells. The CD8(bright+)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 β1-integrins in CD8(bright+)CD28- T-cells and indicate that CD8(bright+) CD28- T cells have a restricted Th1 cytokine repertoire.

Publication Title

Scandinavian Journal of Immunology