title: CD26-mediated co-stimulation in human CD8(+)  T cells provokes effector function via pro-inflammatory cytokine production.
abstract: 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.
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatano
authors.forename: Kei
authors.initials: K
authors.lastname: Ohnuma
authors.forename: Junpei
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
mesh_terms: D000917:Antibody Formation / Q000502:physiology; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007156:Immunologic Memory / Q000502:physiology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D016207:Cytokines; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; C509213:GZMB protein, human; D053804:Granzymes