title: ICOS co-stimulatory receptor is essential for T-cell activation and function.
abstract: T-lymphocyte activation and immune function are regulated by co-stimulatory molecules. CD28, a receptor for B7 gene products, has a chief role in initiating T-cell immune responses. CTLA4, which binds B7 with a higher affinity, is induced after T-cell activation and is involved in downregulating T-cell responses. The inducible co-stimulatory molecule (ICOS), a third member of the CD28/CTLA4 family, is expressed on activated T cells. Its ligand B7H/B7RP-1 is expressed on B cells and in non-immune tissues after injection of lipopolysaccharide into animals. To understand the role of ICOS in T-cell activation and function, we generated and analysed ICOS-deficient mice. Here we show that T-cell activation and proliferation are defective in the absence of ICOS. In addition, ICOS -/- T cells fail to produce interleukin-4 when differentiated in vitro or when primed in vivo. ICOS is required for humoral immune responses after immunization with several antigens. ICOS-/- mice showed greatly enhanced susceptibility to experimental autoimmune encephalomyelitis, indicating that ICOS has a protective role in inflammatory autoimmune diseases.
authors.affiliation: Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: C
authors.initials: C
authors.lastname: Dong
authors.forename: A E
authors.initials: AE
authors.lastname: Juedes
authors.forename: U A
authors.initials: UA
authors.lastname: Temann
authors.forename: S
authors.initials: S
authors.lastname: Shresta
authors.forename: J P
authors.initials: JP
authors.lastname: Allison
authors.forename: N H
authors.initials: NH
authors.lastname: Ruddle
authors.forename: R A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D018390:Gene Targeting; D006433:Hemocyanins / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D018793:Interleukin-13; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D015847:Interleukin-4; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin