title: ICOS controls the pool size of effector-memory and regulatory T cells.
abstract: ICOS is an important regulator of T cell effector function. ICOS-deficient patients as well as knockout mice show severe defects in T cell-dependent B cell responses. Several in vitro and in vivo studies attributed this phenomenon to impaired up-regulation of cell surface communication molecules and cytokine synthesis by ICOS-deficient T cells. However, we now could show with Ag-specific T cells in a murine adoptive transfer system that signaling via ICOS does not significantly affect early T cell activation. Instead, ICOS substantially contributes to the survival and expansion of effector T cells upon local challenge with Ag and adjuvant. Importantly, the observed biological function of ICOS also extends to FoxP3+ regulatory T cells, as can be observed after systemic Ag delivery without adjuvant. In line with these findings, absence of ICOS under homeostatic conditions of nonimmunized mice leads to a reduced number of both effector-memory and FoxP3+ regulatory T cells. Based on these results, we propose a biological role for ICOS as a costimulatory, agonistic molecule for a variety of effector T cells with differing and partly opposing functional roles. This concept may reconcile a number of past in vivo studies with seemingly contradictory results on ICOS function.
authors.affiliation: Molecular Immunology, Robert Koch Institute, Berlin, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Burmeister
authors.forename: Timo
authors.initials: T
authors.lastname: Lischke
authors.forename: Anja C
authors.initials: AC
authors.lastname: Dahler
authors.forename: Hans Werner
authors.initials: HW
authors.lastname: Mages
authors.forename: Kong-Peng
authors.initials: KP
authors.lastname: Lam
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kroczek
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002452:Cell Count; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein