title: Stat5a/b are essential for normal lymphoid development and differentiation.
abstract: Cytokines that use the common gamma chain gammac are critical for lymphoid development and function. Mutations of the IL-7 receptor, gammac, or its associated kinase, Jak3, are the major cause of human severe combined immunodeficiency. Although activated by IL-7, Stat5a/b (Stat, signal transducer and activator of transcription) have been thought to play limited roles in lymphoid development. However, we now show that mice completely deficient in Stat5a/b have severely impaired lymphoid development and differentiation. Absence of Stat5 also abrogates T cell receptor gamma rearrangement and survival of peripheral CD8(+) T cells. Thus, deficiency of Stat5 results in severe combined immunodeficiency, similar in many respects to deficiency of IL-7R, gammac, and Jak3.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Yao
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Cui
authors.forename: Wendy T
authors.initials: WT
authors.lastname: Watford
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hissong
authors.forename: Denise
authors.initials: D
authors.lastname: Li
authors.forename: Scott K
authors.initials: SK
authors.lastname: Durum
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jiang
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002454:Cell Differentiation; D049109:Cell Proliferation; D017690:Cell Transplantation; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D053616:Janus Kinase 3; D008099:Liver / Q000196:embryology; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000196:embryology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D018960:Hyaluronan Receptors; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D012313:RNA; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3