ICOS co-stimulatory receptor is essential for T-cell activation and function

• Published in: Nature (London) 2001-01, Vol.409 (6816), p.97-101
• Main Authors: Flavell, Richard A, Dong, Chen, Juedes, Amy E, Temann, Ulla-Angela, Shresta, Sujan, Allison, James P, Ruddle, Nancy H
• Format: Article
• Language: English
• Subjects: AB7 antigen; Amino Acid Sequence; Animals; Antibody Formation; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - physiology; B7 antigen; Biological and medical sciences; CD28 antigen; Cell Differentiation; Cells; Cells, Cultured; CTLA-4 protein; Encephalomyelitis, Autoimmune, Experimental - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Targeting; Genes; Hemocyanins - immunology; Humanities and Social Sciences; ICOS gene; ICOS protein; Immune response; Immunization; Immunobiology; Immunology; Inducible T-Cell Co-Stimulator Protein; Interleukin-13 - biosynthesis; Interleukin-4 - biosynthesis; letter; Lymph Nodes - pathology; Lymphocyte Activation; Lymphocytes; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Knockout; Molecular Sequence Data; Molecules; multidisciplinary; Myelin Proteins; Myelin-Associated Glycoprotein - immunology; Myelin-Oligodendrocyte Glycoprotein; Rodents; Science; Science (multidisciplinary); T-Lymphocytes - cytology; T-Lymphocytes - immunology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35051100

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.