Thymocytes in Thy-1-/- mice show augmented TCR signaling and impaired differentiation.
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.
Hueber
A O
AO
Center d'Immunologie INSERM-CNRS de Marseille Luminy, Case 906, 13288 Marseille Cedex 9, France.
Bernard
A M
AM
Battari
C L
CL
Marguet
D
D
Massol
P
P
Foa
C
C
Brun
N
N
Garcia
S
S
Stewart
C
C
Pierres
M
M
He
H T
HT
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
D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens