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      Cloning of the Murine Thymic Stromal Lymphopoietin (Tslp) Receptor : Formation of a Functional Heteromeric Complex Requires Interleukin 7 Receptor

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          Abstract

          The cellular receptor for murine thymic stromal lymphopoietin (TSLP) was detected in a variety of murine, but not human myelomonocytic cell lines by radioligand binding. cDNA clones encoding the receptor were isolated from a murine T helper cell cDNA library. TSLP receptor (TSLPR) is a member of the hematopoietin receptor family. Transfection of TSLPR cDNA resulted in only low affinity binding. Cotransfection of the interleukin 7 (IL-7)Rα chain cDNA resulted in conversion to high affinity binding. TSLP did not activate cells from IL-7Rα −/− mice, but did activate cells from γc −/− mice. Thus, the functional TSLPR requires the IL-7Rα chain, but not the γc chain for signaling.

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          A new method for predicting signal sequence cleavage sites.

          G von Heijne (1986)
          A new method for identifying secretory signal sequences and for predicting the site of cleavage between a signal sequence and the mature exported protein is described. The predictive accuracy is estimated to be around 75-80% for both prokaryotic and eukaryotic proteins.
          Article 0 comments Cited 314 times – based on 0 reviews     Review now
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            Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice

            JD Meyer, KH Grabstein, JJ Peschon … (1994)
            Interleukin 7 (IL-7) stimulates the proliferation of B cell progenitors, thymocytes, and mature T cells through an interaction with a high affinity receptor (IL-7R) belonging to the hematopoietin receptor superfamily. We have further addressed the role of IL-7 and its receptor during B and T cell development by generating mice genetically deficient in IL-7R. Mutant mice display a profound reduction in thymic and peripheral lymphoid cellularity. Analyses of lymphoid progenitor populations in IL-7R-deficient mice define precisely those developmental stages affected by the mutation and reveal a critical role for IL-7R during early lymphoid development. Significantly, these studies indicate that the phase of thymocyte expansion occurring before the onset of T cell receptor gene rearrangement is critically dependent upon, and mediated by the high affinity receptor for IL-7.
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              Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain.

              James DiSanto, D Grand, K Rajewsky … (1995)
              The interleukin 2 receptor gamma chain (IL-2R gamma) is a component of the receptors for IL-2, IL-4, IL-7, and IL-15. Mutations in IL-2R gamma in man appear responsible for the X chromosome-linked immunodeficiency SCIDX1, characterized by a defect in T-cell and natural killer (NK)-cell differentiation with the presence of poorly functioning B cells. To explore at which level IL-2R gamma affects lymphoid development in vivo, we have analyzed mice derived from embryonic stem (ES) cells with mutant IL-2R gamma loci generated by Cre/loxP-mediated recombination. In the peripheral blood of chimeric animals, lymphoid cells derived from IL-2R gamma- ES cells were not detected, although control ES cells carrying an IL-2R gamma gene with embedded loxP sites gave rise to T-, B-, and NK-cell lineages. Germline IL-2R gamma-deficient male animals, however, developed some mature splenic B and T cells, although the absolute number of lymphocytes was almost 10-fold reduced. In contrast, there was a complete disappearance of NK cells (over 350-fold reduction). Development of gut-associated intraepithelial lymphocytes was also severely diminished, and Peyer's patches were not detected. In vitro mitogenic responses of thymocytes, IL-4-directed immunoglobulin class switch of splenocytes, and NK activity were defective. Thus, IL-2R gamma facilitates mainstream B- and T-cell generation and function and also appears to be essential for NK-cell development.
              Article 0 comments Cited 128 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                :
                Immunex Corporation, 51 University St., Seattle, WA 98101.206-233-9733206-587-0430
                Journal
                Journal ID (nlm-ta): J Exp Med
                Title: The Journal of Experimental Medicine
                Publisher: The Rockefeller University Press
                ISSN (Print): 0022-1007
                ISSN (Electronic): 1540-9538
                Publication date (Print): 5 September 2000
                Volume: 192
                Issue: 5
                Pages: 659-670
                Affiliations
                [a ]Department of Biochemistry, Department of Biological Sciences, and the Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101
                [b ]Departement d'Immunologie, Institut Pasteur, 75724 Paris, France
                [c ]Institute for Genetics, Cologne D-50931, Germany
                [d ]Mammalian Genetics Laboratory, ABL-Basic Research Program National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, Maryland 21702
                [e ]Department of Biological Structure, University of Washington, Seattle, Washington 98195
                [f ]Virginia Mason Research Center, Seattle, Washington 98101
                Article
                Publisher ID: 992102
                DOI: 10.1084/jem.192.5.659
                PMC ID: 2193276
                PubMed ID: 10974032
                SO-VID: d8687e3a-dfb7-4904-8ff0-148fe840a713
                Copyright © © 2000 The Rockefeller University Press
                History
                Date received : 23 November 1999
                Date revision requested : 12 June 2000
                Date accepted : 22 June 2000
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Medicine
                Keywords: cytokine receptors,dna sequence,interleukin 2 receptor,cytokine,interleukin 7 receptor
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: cytokine receptors, dna sequence, interleukin 2 receptor, cytokine, interleukin 7 receptor

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