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

摘要

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 CD26high 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.