CD26‐mediated co‐stimulation in human CD8+ T cells provokes effector function via pro‐inflammatory cytokine production

CD26 is an activation marker of human CD4⁺ T cells, and is associated with T‐cell signal transduction processes as a co‐stimulatory molecule. We have previously demonstrated that high CD26 cell surface expression on CD4⁺ T cells is correlated with the production of T helper type 1 cytokines, whereas CD26⁺ T helper cells stimulate antibody synthesis in B cells. Although the cellular and molecular mechanisms involved in CD26‐mediated CD4⁺ T‐cell activation have been extensively evaluated by our group and others, the role of CD26 in CD8⁺ T cells has not been clearly elucidated. In the present study, we examine the effector function of CD8⁺ T cells via CD26‐mediated co‐stimulation in comparison with CD28‐mediated co‐stimulation. We found that CD26^high CD8⁺ T cells belong to the early effector memory T‐cell subset, and that CD26‐mediated co‐stimulation of CD8⁺ T cells exerts a cytotoxic effect preferentially via granzyme B, tumour necrosis factor‐α, interferon‐γ and Fas ligand. The effector function associated with CD26‐mediated co‐stimulation is enhanced compared with that obtained through CD28‐mediated co‐stimulation, suggesting that the CD26 co‐stimulation pathway in CD8⁺ T cells is distinct from the CD28 co‐stimulation pathway. Targeting CD26 in CD8⁺ T cells therefore has the potential to be useful in studies of immune responses to new vaccine candidates as well as innovative therapy for immune‐mediated diseases.