Overexpression of suppressor of cytokine signaling-1 impairs pre-T-cell receptor-induced proliferation but not differentiation of immature thymocytes

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 suppr essor of cytokine signaling-1 (SOCS-1), which acts as a negative regulator of Janus kinases, SOCS-1 is normally expressed throughout thymocyte develop ment; however, retroviral-mediated overexpression of SOCS-1 in fetal liver- derived hematopoietic progenitors prevented their progression beyond the ea rliest stage of T-cell development. Further analysis revealed that SOCS-1 e xpression is transiently suppressed following pre-T-cell receptor (TCR) sig naling. Moreover, constitutive expression of SOCS-1 abrogated pre-TCR-media ted expansion of immature thymocytes but did not interfere with differentia tion. These findings reveal that SOCS-1 serves to regulate cytokine signali ng at critical checkpoints during early T-cell development. (Blood, 2001;97 :2269-2277) (C) 2001 by The American Society of Hematology.