title: Interleukin-7 is required for CD4(+) T cell activation and autoimmune neuroinflammation.
abstract: IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4(+) T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4(+) T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4(+) T cell activation and that IL-7R antagonism may be effective in treating CD4(+) T cell-mediated neuroinflammation and other autoimmune inflammatory conditions.
authors: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Brian R
authors: BR
authors: Lawson
authors: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Rosana
authors: R
authors: Gonzalez-Quintial
authors: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Theodoros
authors: T
authors: Eleftheriadis
authors: University of Minnesota, Department of Laboratory Medicine and Pathology, 2-116 MBB, 2101 6th Street SE, Minneapolis, MN 55414, USA.
authors: Michael A
authors: MA
authors: Farrar
authors: Northwestern University Medical School, Department of Microbiology-Immunology, 303 E Chicago Avenue, Chicago, IL 60611, USA.
authors: Stephen D
authors: SD
authors: Miller
authors: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Karsten
authors: K
authors: Sauer
authors: National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, MD 20892, USA.
authors: Dorian B
authors: DB
authors: McGavern
authors: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Dwight H
authors: DH
authors: Kono
authors: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Roberto
authors: R
authors: Baccala
authors: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: argyrio@scripps.edu.
authors: Argyrios N
authors: AN
authors: Theofilopoulos
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015851:Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000276:immunology / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D016207:Cytokines; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D050795:STAT2 Transcription Factor; C415350:interleukin-7 receptor, alpha chain; D051057:Proto-Oncogene Proteins c-akt
keywords: EAE; IL-7; Signaling pathways; T cells