Document 0266
 DOCN  M9590266
 TI    Signal transduction by the cytokine receptor common gamma chain.
       Implications for HIV immunopathogenesis.
 DT    9509
 AU    Williamson P; Gaulton G; Henthorn P; Department of Immunology, Westmead
       Hospital.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:256 (unnumbered poster).
       Unique Identifier : AIDSLINE ASHM6/95291833
 AB    Recent cloning of the cytokine receptor common gamma chain (gamma c),
       and identification of its role in T-cell development and response,
       allows speculation that any perturbations of gamma c function caused by
       HIV would contribute greatly to CD4 cell dysfunction. Defects in gamma c
       function lead to signal transduction malfunctions in the IL-2, IL-4 and
       IL-7 receptors, and inherited mutations of the gamma c gene are
       associated with a severe T-cell immunodeficiency, called X-SCID. The
       gamma c protein is 360 amino acids in length, and has an 86 amino acid
       cytoplasmic domain containing an SH2-like domain that has been
       implicated in signal transduction. To study the role of gamma c, we have
       established an in vitro correlate of X-SCID using Hela cells tranfected
       with IL-2R alpha and IL-2R beta. We have characterised signalling
       defects in these cells, and shown that signalling functions can be
       reconstituted by gamma c gene transfer. Four IL-2R gamma cDNA constructs
       have been cloned into LX-series retroviral vectors. Recombinant
       retrovirus from one of these has been produced in the amphotropic
       packaging cell line, PG13. Four of 17 amphotropic clones producing the
       recombinant retrovirus have been transduced into HeLa alpha/beta cells.
       Expression of gamma c mRNA in these cells was confirmed by RT-PCR The
       cells bound IL-2 with apparent high affinity, and showed significant
       increases in tyrosine kinase activity in response to IL-2. On the basis
       of these studies, two viruses have been selected for gene therapy
       studies in an animal model, and bone marrow transduction studies have
       commenced. Implications of these studies to the of HIV will be
       discussed.
 DE    Animal  Cloning, Molecular  Gene Transfer  Hela Cells  Human
       HIV/*IMMUNOLOGY  HIV Infections/*IMMUNOLOGY  Lymphocyte
       Transformation/GENETICS/*IMMUNOLOGY  Receptors,
       Cytokine/GENETICS/*PHYSIOLOGY  Severe Combined
       Immunodeficiency/IMMUNOLOGY  Signal Transduction/GENETICS/*IMMUNOLOGY
       T-Lymphocytes/*IMMUNOLOGY  MEETING ABSTRACT

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       protected by Copyright Law (Title 17, U.S.Code).