title: ICOS+ Th cells produce distinct cytokines in different mucosal immune responses.
abstract: T cell activation, differentiation and effector functions depend on signals delivered through the antigen-specific TCR and non-clonal costimulatory receptors on the T cell. Activated T cells express the inducible costimulator (ICOS). We examined the co-expression of ICOS with Th cytokines in mucosal immune responses. ICOS+CD4+ Th cells expressed strikingly different cytokines depending on the type of infection encountered and the cells' anatomical localization. In the Th2-dominated response to Schistosoma mansoni, ICOS expression of CD4+ cells isolated from the liver was strongly associated with the expression of IL-5, IL-10, IL-13, and T1/ST2, but not with the chemokine receptor CXCR5, a pattern consistent with Th2 effector cells. In the secondary lymphatic organs of schistosome-infected mice, ICOS expression was randomly correlated with Th2 effector-cytokines, but positively correlated with CXCR5 expression; a pattern consistent with follicular Th cells. In Th cells isolated from gut or liver of mice infected with Toxoplasma gondii, ICOS expression was positively correlated with IFN-gamma production. Finally, in the severe combined immunodeficiency transfer colitis model, ICOS expression was strongly positively associated with IFN-gamma and IL-2. Thus, ICOS appears to costimulate distinct effector functions in different immune responses, depending on factors such as the nature of the antigen encountered and localization and chronicity of the immune response.
authors.affiliation: Deutsches Rheumaforschungzentrum, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bonhagen
authors.forename: Oliver
authors.initials: O
authors.lastname: Liesenfeld
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Stadecker
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
authors.forename: Klaus
authors.initials: K
authors.lastname: Erb
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kroczek
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003092:Colitis / Q000276:immunology; D004064:Digestive System / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D018928:Immunity, Mucosal / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008168:Lung / Q000276:immunology / Q000469:parasitology; D008221:Lymphoid Tissue / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D009559:Nippostrongylus; D009928:Organ Specificity; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D018123:Receptors, Interleukin; D012555:Schistosomiasis mansoni / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D017206:Strongylida Infections / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C513179:CXCR5 protein, mouse; C556694:Icos protein, mouse; C486189:Il1rl1 protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D007376:Interleukin-2; D015848:Interleukin-5; D008222:Lymphokines; D008565:Membrane Proteins; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D016753:Interleukin-10; D007371:Interferon-gamma