Eynon E E, Livák F, Kuida K, Schatz D G, Flavell R A
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 1999 Feb 1;162(3):1448-59.
Janus kinase 3 (Jak3) plays a central role in the transduction of signals mediated by the IL-2 family of cytokine receptors. Targeted deletion of the murine Jak3 gene results in severe reduction of alphabeta and complete elimination of gammadelta lineage thymocytes and NK cells. The developmental blockade appears to be imposed on early thymocyte differentiation and/or expansion. In this study, we show that bcl-2 expression and in vivo survival of immature thymocytes are greatly compromised in Jak3-/- mice. There is no gross deficiency in rearrangements of the TCRdelta and certain gamma loci in pre-T cells, and a functional gammadelta TCR transgene cannot rescue gammadelta lineage differentiation in Jak3-/- mice. In contrast, a TCRbeta transgene is partially able to restore alphabeta thymocyte development. These data suggest that the signals mediated by Jak3 are critical for survival of all thymocyte precursors particularly during TCRbeta-chain gene rearrangement, and are continuously required in the gammadelta lineage. The results also emphasize the fundamentally different requirements for differentiation of the alphabeta and gammadelta T cell lineages.
Janus激酶3（Jak3）在白细胞介素-2细胞因子受体家族介导的信号转导中起核心作用。靶向缺失小鼠Jak3基因会导致αβ谱系胸腺细胞严重减少，γδ谱系胸腺细胞和自然杀伤细胞完全消失。这种发育阻滞似乎发生在早期胸腺细胞分化和/或增殖阶段。在本研究中，我们发现Jak3基因敲除小鼠中未成熟胸腺细胞的bcl-2表达和体内存活能力受到极大损害。前T细胞中TCRδ和某些γ基因座的重排没有明显缺陷，功能性γδTCR转基因无法挽救Jak3基因敲除小鼠中的γδ谱系分化。相反，TCRβ转基因能够部分恢复αβ胸腺细胞的发育。这些数据表明，Jak3介导的信号对于所有胸腺细胞前体的存活至关重要，尤其是在TCRβ链基因重排期间，并且在γδ谱系中持续需要。结果还强调了αβ和γδT细胞谱系分化的根本不同要求。
