title: T-lymphocyte differentiation and proliferation in the absence of the cytoplasmic tail of the common cytokine receptor gamma c chain in a severe combined immune deficiency X1 patient.
abstract: Mutation of the gamma c chain common to interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15 receptors has been shown to be responsible for the X chromosome-linked severe combined immune deficiency (SCIDX1). Human SCIDX1 patients are characterized by an absence of T and natural killer cell differentiation. We report the case of a SCIDX1 patient who first had few detectable peripheral T cells, then developed, after haploidentical T-depleted bone marrow transplantation (BMT), up to 2,000/microL autologous T cells. These T cells have persisted over 8 years after BMT and were able to proliferate in the presence of mitogens and of some antigens, although to a lesser extent than control T cells. A stop mutation was identified which predicts that the major part of the cytoplasmic tail of gamma c is truncated. This mutation does not affect high-affinity IL-2 binding, but it partly decreases IL-2 endocytosis and prevents the downmodulation of the IL-2-receptor beta chain and the tyrosine phosphorylation of Jak 3 protein in response to IL-2. This report raises questions concerning the role of the gamma c chain in IL-2 receptor endocytosis and in T-cell development and differentiation.
authors.affiliation: Unité de Biologie des Interactions Cellulaires, URA CNRS 1960, Institut Pasteur, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Morelon
authors.forename: A
authors.initials: A
authors.lastname: Dautry-Varsat
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: S
authors.initials: S
authors.lastname: Hacein-Bay
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: G
authors.initials: G
authors.lastname: de Saint Basile
mesh_terms: D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002455:Cell Division; D002678:Chimera; D004705:Endocytosis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000378:metabolism; D053616:Janus Kinase 3; D018655:Lymphocyte Count; D008297:Male; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000737:chemistry* / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000473:pathology*; D014960:X Chromosome
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3