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Blood, 15 April 2001, Vol. 97, No. 8, pp. 2269-2277
HEMATOPOIESIS
Overexpression of suppressor of cytokine signaling-1 impairs
pre-T-cell receptor-induced proliferation but not differentiation of
immature thymocytes
Sébastien Trop,
Paulo De Sepulveda,
Juan Carlos Zúñiga-Pflücker, and
Robert Rottapel
From the Departments of Immunology, Medicine, and
Medical Biophysics, University of Toronto; Ontario Cancer Institute,
Princess Margaret Hospital; both of Toronto, Canada; and Department of
Medicine, Division of Experimental Medicine, McGill University,
Montréal, QC, Canada.
Cytokines play an essential role during early T-cell development.
However, the mechanisms controlling cytokine signaling in developing
thymocytes have not been elucidated. Cytokine receptor signaling can be
modulated by suppressor of cytokine signaling-1 (SOCS-1), which acts as
a negative regulator of Janus kinases. SOCS-1 is normally expressed
throughout thymocyte development; however, retroviral-mediated
overexpression of SOCS-1 in fetal liver-derived hematopoietic
progenitors prevented their progression beyond the earliest stage of
T-cell development. Further analysis revealed that SOCS-1 expression is
transiently suppressed following pre-T-cell receptor (TCR) signaling.
Moreover, constitutive expression of SOCS-1 abrogated
pre-TCR- mediated expansion of immature thymocytes but
did not interfere with differentiation. These findings reveal that
SOCS-1 serves to regulate cytokine signaling at critical checkpoints
during early T-cell development.
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