title: Expression of ICOS in vivo defines CD4+ effector T cells with high inflammatory potential and a strong bias for secretion of interleukin 10.
abstract: The studies performed to date analyzed the overall participation of the inducible costimulator (ICOS) in model diseases, but did not yield information on the nature and function of ICOS-expressing T cells in vivo. We examined ICOS(+) T cells in the secondary lymphoid organs of nonmanipulated mice, in the context of an "unbiased" immune system shaped by environmental antigens. Using single cell analysis, ICOS(low) cells were found to be loosely associated with the early cytokines interleukin (IL)-2, IL-3, IL-6, and interferon (IFN)-gamma. ICOS(medium) cells, the large majority of ICOS(+) T cells in vivo, were very tightly associated with the synthesis of the T helper type 2 (Th2) cytokines IL-4, IL-5, and IL-13, and these cells exhibited potent inflammatory effects in vivo. In contrast, ICOS(high) T cells were highly and selectively linked to the anti-inflammatory cytokine IL-10. Overall, these data seem to indicate that ICOS cell surface density serves as a regulatory mechanism for the release of cytokines with different immunological properties. Further in vivo functional experiments with in vitro-activated T cells strongly suggested that the ICOS(+) population, although representing in vivo only around 10% of T cells bearing early or late activation markers, nevertheless encompasses virtually all effector T cells, a finding with major diagnostic and therapeutic implications.
authors.affiliation: Deutsches Rheumaforschungszentrum, Schumannstrasse 21/22, D-10117 Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
authors.forename: Tilmann
authors.initials: T
authors.lastname: Kallinich
authors.forename: Hans Werner
authors.initials: HW
authors.lastname: Mages
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bonhagen
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Eckard
authors.initials: E
authors.lastname: Hamelmann
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kroczek
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D066298:In Vitro Techniques; D060889:Inducible T-Cell Co-Stimulator Protein; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D018836:Inflammation Mediators; D016753:Interleukin-10; D010047:Ovalbumin