Thomis D C, Berg L J
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
J Exp Med. 1997 Jan 20;185(2):197-206. doi: 10.1084/jem.185.2.197.
The Jak family tyrosine kinase, Jak3, is involved in signaling through cytokine receptors that utilize the common gamma chain (gammac), such as those for IL-2, IL-4, IL-7, IL-9, and IL-15. Recent studies of Jak3-deficient mice and humans have demonstrated that Jak3 plays a critical role in B and T lymphocyte maturation and function. The T lymphocyte defects in Jak3-deficient mice include a small thymus, a decrease in peripheral CD8+ cells, an increase in the surface expression of activation markers, and a severe reduction in proliferative and cytokine secretion responses to mitogenic stimuli. To determine whether the peripheral T lymphocyte defects result from aberrant maturation in the thymus or from the absence of Jak3 protein in peripheral T cells, we generated reconstituted mice that express normal levels of Jak3 protein in the thymus but lose Jak3 expression in peripheral T cells. Jak3 expression in the thymus restores normal T cell development, including CD8+, gammadelta, and natural killer cells. However, the loss of Jak3 protein in peripheral T cells leads to the Jak3-/- phenotype, demonstrating that Jak3 is constitutively required to maintain T cell function.
Jak家族酪氨酸激酶Jak3参与通过利用共同γ链（γc）的细胞因子受体进行的信号传导，这些受体如白细胞介素-2、白细胞介素-4、白细胞介素-7、白细胞介素-9和白细胞介素-15的受体。最近对Jak3缺陷小鼠和人类的研究表明，Jak3在B和T淋巴细胞的成熟及功能中起关键作用。Jak3缺陷小鼠的T淋巴细胞缺陷包括胸腺较小、外周CD8+细胞减少、活化标志物的表面表达增加以及对有丝分裂原刺激的增殖和细胞因子分泌反应严重降低。为了确定外周T淋巴细胞缺陷是由于胸腺中异常成熟还是由于外周T细胞中缺乏Jak3蛋白所致，我们构建了在胸腺中表达正常水平的Jak3蛋白但在外周T细胞中失去Jak3表达的重建小鼠。胸腺中Jak3的表达恢复了正常的T细胞发育，包括CD8+、γδ和自然杀伤细胞。然而，外周T细胞中Jak3蛋白的缺失导致了Jak3 -/- 表型，表明Jak3是维持T细胞功能所必需的。
