title: Costimulation of CD28- T cells through CD3 and beta1-integrins induces a limited Th1 cytokine response.
abstract: 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.
authors.affiliation: The Pulmonary Center, Boston University Medical School, Boston, MA, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Saukkonen
authors.forename: A
authors.initials: A
authors.lastname: Tantri
authors.forename: J
authors.initials: J
authors.lastname: Berman
mesh_terms: D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005353:Fibronectins / Q000276:immunology; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D017469:Receptors, Fibronectin / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007376:Interleukin-2; D017469:Receptors, Fibronectin; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing; D016753:Interleukin-10; D007371:Interferon-gamma