Bazdar Douglas A, Kalinowska Magdalena, Sieg Scott F
Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, and University Hospitals, Cleveland, Ohio 44106, USA.
J Infect Dis. 2009 Apr 1;199(7):1019-28. doi: 10.1086/597210.
Loss of interleukin-7 (IL-2) receptor expression has been described in T lymphocytes from persons with human immunodeficiency virus (HIV) infection, potentially contributing to perturbations in T cell homeostasis. We investigated IL-7 receptor signaling by measuring signal transducer and activator of transcription 5 (STAT5) phosphorylation in CD4+ T cell subsets from HIV-infected persons. We determined that CD45RA- memory cell subsets (both CD27+ and CD27-) displayed the most robust immediate responses to IL-7, whereas naive CD4+ T cells sustained the signal most efficiently. Memory CD4+ T cells with a terminal phenotype (CD45RA+CD27-) responded poorly to IL-7 stimulation. Defects in signaling were observed in cells from viremic HIV-infected persons and were especially pronounced in CD45RA-CD27- memory subset. Although CD127 expression was diminished for T cells from HIV-infected persons, it was not directly related to IL-7 receptor signaling function. Instead, age was inversely related to IL-7 signaling in cells from both HIV-infected viremic subjects and healthy control subjects. Thus, HIV infection results in impaired IL-7 responsiveness, especially in memory CD4+ T cells, and this defect is likely compounded by aging.
在人类免疫缺陷病毒（HIV）感染者的T淋巴细胞中，已发现白细胞介素-7（IL-7）受体表达缺失，这可能导致T细胞稳态紊乱。我们通过测量HIV感染者CD4 + T细胞亚群中信号转导及转录激活因子5（STAT5）的磷酸化来研究IL-7受体信号传导。我们确定，CD45RA - 记忆细胞亚群（CD27 +和CD27 - ）对IL-7表现出最强有力的即时反应，而初始CD4 + T细胞维持信号的效率最高。具有终末表型（CD45RA + CD27 - ）的记忆CD4 + T细胞对IL-7刺激反应不佳。在病毒血症期HIV感染者的细胞中观察到信号传导缺陷，在CD45RA - CD27 - 记忆亚群中尤为明显。尽管HIV感染者的T细胞中CD127表达减少，但它与IL-7受体信号传导功能无直接关系。相反，年龄与病毒血症期HIV感染者和健康对照者细胞中的IL-7信号传导呈负相关。因此，HIV感染导致IL-7反应性受损，尤其是在记忆CD4 + T细胞中，并且这种缺陷可能因衰老而加剧。
