title: Modulation of CD103 expression on human colon carcinoma-specific CTL.
abstract: Recent results have shown a correlation between survival and frequency of tumor-infiltrating T cells in colorectal cancer patients. However, the mechanisms controlling the ability of human T lymphocytes to infiltrate colon carcinoma remain unclear. Although, it is known that expression of the integrin CD103alpha(E)/beta(7) by intraepithelial lymphocytes controls the retention of lymphocytes in epithelial layers, very little is known about the expression of intestinal homing receptors in human T lymphocytes. In particular, it remains unknown whether expression of CD103/beta(7) by human colon cancer-specific T lymphocytes is controlled by recognition of tumor Ags and is imprinted during T cell priming, facilitating its expression during memory T cell activation. In this study, we demonstrate that expression of CD103/beta(7) in human colon carcinoma-specific CTL is synergistically enhanced by the simultaneous TGF-beta1 stimulation and Ag recognition. These results were confirmed by using a panel of human CTL clones. Finally, we show that priming of naive CD8(+) T cells in the presence of TGF-beta1 ensures up-regulation of CD103/beta(7) in recall responses, at concentrations of TGF-beta1 significantly lower than those required by memory T cells primed in the absence of TGF-beta1. These results indicate a role of TGF-beta1 during T cell priming in modulating expression of CD103/beta(7) and controlling retention of human memory CD8(+) T cells into tumor epithelium.
authors.affiliation: Tumor Immunology Group, Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Khoon-Lin
authors.initials: KL
authors.lastname: Ling
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dulphy
authors.forename: Pru
authors.initials: P
authors.lastname: Bahl
authors.forename: Mariolina
authors.initials: M
authors.lastname: Salio
authors.forename: Kevin
authors.initials: K
authors.lastname: Maskell
authors.forename: Juan
authors.initials: J
authors.lastname: Piris
authors.forename: Bryan F
authors.initials: BF
authors.lastname: Warren
authors.forename: Bruce D
authors.initials: BD
authors.lastname: George
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Mortensen
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007156:Immunologic Memory; D039001:Integrin alpha Chains / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D039001:Integrin alpha Chains; D053773:Transforming Growth Factor beta1; C091367:alpha E integrins