title: Thymocytes in Thy-1-/- mice show augmented TCR signaling and impaired differentiation.
abstract: Thy-1, a single variable-like immunoglobulin superfamily domain anchored in the plasma membrane by a glycosyl phosphaditylinositol tail [1], is a major surface glycoprotein in adult mammalian neurons and rodent thymocytes [2]; the function of Thy-1 has remained enigmatic since its discovery [3]. Studies in vitro have implicated Thy-1 in homotypic and heterotypic cell-cell interactions [2,4]. Ligation of Thy-1 initiates transmembrane signaling pathways that lead to diverse physiological outcomes in different cells [2,5-7]. In rodents, Thy-1 is highly expressed on the surface of CD4+CD8+ double-positive immature thymocytes and downregulated in mature T cells. Here, we report that thymocytes from Thy-1-/- mice [8] had altered cell-cell contacts, and hyperresponsiveness to T-cell receptor (TCR) triggering as demonstrated by the heightened activation of p56lck, phosphorylation of TCR subunits, Ca2+ fluxes and cell proliferation. Thy-1-/- thymocytes exhibited impaired maturation from the double positive to single positive stage of thymocyte development, possibly due to inappropriate negative selection, and were prone to T lymphomas in aged mice. These observations indicate that Thy-1 negatively regulates TCR-mediated signaling and controls activation thresholds during thymocyte differentiation.
authors.affiliation: Center d'Immunologie INSERM-CNRS de Marseille Luminy, Case 906, 13288 Marseille Cedex 9, France.
authors.forename: A O
authors.initials: AO
authors.lastname: Hueber
authors.forename: A M
authors.initials: AM
authors.lastname: Bernard
authors.forename: C L
authors.initials: CL
authors.lastname: Battari
authors.forename: D
authors.initials: D
authors.lastname: Marguet
authors.forename: P
authors.initials: P
authors.lastname: Massol
authors.forename: C
authors.initials: C
authors.lastname: Foa
authors.forename: N
authors.initials: N
authors.lastname: Brun
authors.forename: S
authors.initials: S
authors.lastname: Garcia
authors.forename: C
authors.initials: C
authors.lastname: Stewart
authors.forename: M
authors.initials: M
authors.lastname: Pierres
authors.forename: H T
authors.initials: HT
authors.lastname: He
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D051379:Mice; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D018800:Thy-1 Antigens / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens