title: Alloantigen-induced regulatory CD8+CD103+ T cells.
abstract: Regulatory T cells (Tregs) appear of great importance in the balance between alloreactivity and tolerance and subsets of both CD4(+) and CD8(+) T cells have been recognized to function as regulatory T cells after allogenic transplantation. Among the CD8(+) T-cell subsets, the CD103(+) cells were most recently identified as regulatory. In this review, we describe their phenotypical and functional properties, as well as their relevance for the alloimmune response in vivo. These CD8(+)CD103(+) Tregs are generated within mixed lymphocyte cultures (MLCs) and are elevated by additional transforming growth factor-beta. Interestingly, myeloid dendritic cells are the responsible cell type for induction of CD103(+) Tregs. Allostimulated CD8(+)CD103(+) Tregs display an antigen-experienced effector phenotype with limited effector functions such as cytotoxicity and interferon-gamma production and show a reduced proliferation capacity after restimulation. Beside this anergic phenotype, CD8(+)CD103(+) Tregs are able to suppress alloreactive effector T cells. Through intracellular cytokine staining and transwell assays, we showed that the mechanism of suppression is cytokine independent, but close cell-cell contact is required for suppression.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. S.D.Koch@amc.uva.nl
authors.forename: Sven D
authors.initials: SD
authors.lastname: Koch
authors.forename: Elena
authors.initials: E
authors.lastname: Uss
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D017635:Clonal Anergy / Q000276:immunology*; D006801:Humans; D039001:Integrin alpha Chains / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D007519:Isoantigens; D016212:Transforming Growth Factor beta; C091367:alpha E integrins; D007371:Interferon-gamma