title: Interleukin 7 receptor engagement stimulates tyrosine phosphorylation, inositol phospholipid turnover, proliferation, and selective differentiation to the CD4 lineage by human fetal thymocytes.
abstract: The purposes of this study were to elucidate the effects of recombinant human interleukin 7 (rhIL-7) on proliferation as well as differentiation of human fetal thymocytes and to analyze the biochemical nature of the IL-7 receptor-linked transmembrane signal. In the absence of costimulants, rhIL-7 stimulated the in vitro proliferation and colony formation of CD4+CD8+ double-positive immature fetal thymocytes. Furthermore, rhIL-7 promoted partial differentiation of immature thymocytes with a selective advantage for the development of CD4+CD8- single-positive thymocytes. Our observations suggest that IL-7 likely has an important regulatory role during the earliest stages of human T-cell ontogeny. Stimulation of fetal thymocytes with rhIL-7 resulted in enhanced tyrosine phosphorylation of three distinct phosphoproteins with molecular masses of 72, 98, 123, and 190 kDa and induced a rapid and biphasic increase in the production of inositol 1,4,5-trisphosphate, which was inhibitable by the tyrosine protein kinase inhibitor genistein. Thus, the transmembrane signal triggered by engagement of the IL-7 receptor is intimately linked to a functional tyrosine protein kinase pathway and stimulates the inositol phospholipid turnover and proliferation, as well as selective differentiation to the CD4 lineage, by human fetal thymocytes.
authors.affiliation: Tumor Immunology Laboratory, University of Minnesota Health Sciences Center, Minneapolis 55455.
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
authors.forename: L
authors.initials: L
authors.lastname: Tuel-Ahlgren
authors.forename: V
authors.initials: V
authors.lastname: Obuz
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.forename: I
authors.initials: I
authors.lastname: Dibirdik
authors.forename: M
authors.initials: M
authors.lastname: Hanson
authors.forename: M C
authors.initials: MC
authors.lastname: Langlie
authors.forename: J A
authors.initials: JA
authors.lastname: Ledbetter
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004789:Enzyme Activation; D005333:Fetus; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D015851:Interleukin-7 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology*; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology*; D014443:Tyrosine
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015704:CD4 Antigens; D016207:Cytokines; D015851:Interleukin-7; D007378:Interleukins; D010716:Phosphatidylinositols; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases