Suzuki K, Nakajima H, Saito Y, Saito T, Leonard W J, Iwamoto I
Department of Internal Medicine II, Chiba University School of Medicine, Chiba 260-8670, Japan.
Int Immunol. 2000 Feb;12(2):123-32. doi: 10.1093/intimm/12.2.123.
The common cytokine receptor gamma chain (gamma(c)) is an essential receptor component for IL-2, IL-4, IL-7, IL-9 and IL-15, and thereby gamma(c)-deficient mice exhibit impaired T cell and B cell development. The Janus family tyrosine kinase 3 (Jak3) is known to be associated with gamma(c), and the reported phenotypes of gamma(c)-deficient (gamma(c)(-)) and Jak3-deficient (Jak3(-)) mice are similar, indicating that Jak3 is an essential transducer of gamma(c)-dependent signals. Nevertheless, certain differences have been suggested related to the range of actions of gamma(c) and Jak3. To clarify whether gamma(c)-dependent cytokines can partially transduce their signals without Jak3, we compared lymphocyte development in gamma(c)(-), Jak3(-), and gamma(c) and Jak3 double-deficient (gamma(c)(-)Jak3(-)) mice in the same genetic background. With the exception that T and B cells in Jak3(-) mice express high levels of gamma(c), the defects in thymocyte and peripheral T cell and B cell development are indistinguishable among gamma(c)(-), Jak3(-) and gamma(c)(-)Jak3(-) mice. Interestingly, although Bcl-2 induction was previously suggested to be Jak3-independent, IL-7 cannot induce Bcl-2 expression in CD4 single-positive (SP) thymocytes in either gamma(c)(-) or Jak3(-) mice nor can IL-7 rescue CD4 SP thymocytes from dexamethasone-induced cell death in gamma(c)(-) or Jak3(-) mice. These results indicate that Jak3 is absolutely essential for gamma(c)-dependent T cell and B cell development, and for gamma(c)-dependent prevention of thymocyte apoptosis.
共同细胞因子受体γ链（γ(c)）是白细胞介素-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的重要受体组成部分，因此γ(c)缺陷小鼠表现出T细胞和B细胞发育受损。已知Janus家族酪氨酸激酶3（Jak3）与γ(c)相关，γ(c)缺陷（γ(c)(-)）和Jak3缺陷（Jak3(-)）小鼠的报道表型相似，表明Jak3是γ(c)依赖性信号的重要转导分子。然而，关于γ(c)和Jak3的作用范围已提示存在某些差异。为了阐明γ(c)依赖性细胞因子是否能在没有Jak3的情况下部分转导其信号，我们比较了相同遗传背景下γ(c)(-)、Jak3(-)以及γ(c)和Jak3双缺陷（γ(c)(-)Jak3(-)）小鼠的淋巴细胞发育情况。除了Jak3(-)小鼠中的T细胞和B细胞表达高水平的γ(c)外，γ(c)(-)、Jak3(-)和γ(c)(-)Jak3(-)小鼠的胸腺细胞以及外周T细胞和B细胞发育缺陷并无差异。有趣的是，尽管先前提示Bcl-2的诱导不依赖Jak3，但在γ(c)(-)或Jak3(-)小鼠中，白细胞介素-7均不能诱导CD4单阳性（SP）胸腺细胞中Bcl-2的表达，白细胞介素-7也不能挽救γ(c)(-)或Jak3(-)小鼠中地塞米松诱导的CD4 SP胸腺细胞的细胞死亡。这些结果表明，Jak3对于γ(c)依赖性T细胞和B细胞发育以及γ(c)依赖性预防胸腺细胞凋亡绝对必要。
