title: The common gamma-chain of cytokine receptors regulates intrathymic T cell development at multiple stages.
abstract: Signaling through the common gamma chain (gamma c), a subunit of the receptors for IL-2, -4, -7, -9, and -15, is critical for lymphocyte development, with the IL-7/IL-7R representing one important interaction. To investigate the stages of intrathymic T cell development that are dependent on gamma c and to determine whether gamma c controls T cell development solely as a component of the IL-7R, intrathymic T cell development was compared in IL-7R alpha-deficient mice and anti-gamma c-treated chimeric mice reconstituted with bone marrow and purified pro-T cells. In the presence of anti-gamma c, each of four phenotypically distinguishable stages of CD4- CD8- thymocytes failed to reconstitute T cell development, suggesting that each of these subsets of pro-T cells required gamma c for their differentiation and/or growth. Reconstitution of anti-gamma c-treated chimeric mice with bone marrow from IL-7R alpha-deficient mice indicated that IL-7R only partially contributed to intrathymic T cell development. Furthermore, when compared with IL-7R-deficient mice, anti-gamma c chimeric and gamma c-deficient mice exhibited a distinct phenotypic pattern of pro-T cell development. Collectively, these results indicate that several gamma c-sharing cytokines may contribute to T cell development in the thymus and suggest that one of these cytokines may be novel.
authors.affiliation: Department of Microbiology, University of Miami School of Medicine, FL 33101, USA.
authors.forename: Y W
authors.initials: YW
authors.lastname: He
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.forename: W J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: B
authors.initials: B
authors.lastname: Adkins
authors.forename: T R
authors.initials: TR
authors.lastname: Malek
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005260:Female; D015851:Interleukin-7 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D020395:Receptors, Interleukin-7; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015851:Interleukin-7; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7