Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Infect Dis. 2012 May 1;205(9):1382-90. doi: 10.1093/infdis/jis219. Epub 2012 Mar 26.
Elevated serum interleukin 7 (IL-7) levels are observed in lymphopenic conditions, including idiopathic CD4 lymphopenia (ICL), which is characterized by CD4 lymphopenia in the absence of human immunodeficiency virus infection or other known immunodeficiency.
To test whether defective IL-7 signaling could be an etiologic or contributing factor in ICL, peripheral blood mononuclear cells from patients with ICL (median CD4 T-cell count, 160 cells/μL) and healthy controls (median CD4 T-cell count, 582 cells/μL) were evaluated for expression of IL-7Rα chain (CD127) and intracellular phosphorylated STAT-5 (a marker of γc cytokine signaling) after cytokine stimulation. Gene expression was analyzed by real-time polymerase chain reaction following IL-7 stimulation.
The percentage of CD4+CD127+ T cells was lower in patients with ICL, compared with controls (P < .001). Lower levels of STAT-5 phosphorylation after IL-7 stimulation were observed in both CD4 and CD8 T cells from patients with ICL, compared with controls (P < .001 and P = .017, respectively), that inversely correlated in CD4 T cells with serum IL-7 levels (r = -0.734, P = .013). Destabilization of p27(kip1), a critical step for IL-7-induced T-cell cycling, was decreased in patients with ICL, compared with controls (P = .004), after IL-7 stimulation.
These data suggest that diminished responsiveness to IL-7 in CD4 and CD8 T cells during ICL may be contributing to the dysregulation of T-cell homeostasis.
在淋巴细胞减少症的情况下，包括特发性 CD4 淋巴细胞减少症（ICL），会观察到血清白细胞介素 7（IL-7）水平升高。ICL 的特征是在没有人类免疫缺陷病毒感染或其他已知免疫缺陷的情况下出现 CD4 淋巴细胞减少。
为了测试 IL-7 信号传导缺陷是否是 ICL 的病因或促成因素，评估了 ICL 患者（中位 CD4 T 细胞计数为 160 个/μL）和健康对照者（中位 CD4 T 细胞计数为 582 个/μL）的外周血单核细胞中白细胞介素 7 受体α链（CD127）和细胞内磷酸化 STAT-5（γc 细胞因子信号的标志物）的表达，在细胞因子刺激后。通过实时聚合酶链反应分析 IL-7 刺激后的基因表达。
与对照组相比，ICL 患者的 CD4+CD127+T 细胞百分比较低（P<0.001）。与对照组相比，ICL 患者的 CD4 和 CD8 T 细胞在接受 IL-7 刺激后，STAT-5 磷酸化水平较低（分别为 P<0.001 和 P=0.017），而在 CD4 T 细胞中，血清 IL-7 水平呈负相关（r=-0.734，P=0.013）。与对照组相比，在接受 IL-7 刺激后，ICL 患者的 p27（kip1）（IL-7 诱导 T 细胞循环的关键步骤）失稳减少（P=0.004）。
这些数据表明，在 ICL 期间，CD4 和 CD8 T 细胞对 IL-7 的反应性降低可能导致 T 细胞稳态失调。
