Koesters Sandra A, Alimonti Judie B, Wachihi Charles, Matu Lucy, Anzala Omu, Kimani Joshua, Embree Joanne E, Plummer Francis A, Fowke Keith R
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada, R3E 0 W3.
Eur J Immunol. 2006 Feb;36(2):336-44. doi: 10.1002/eji.200535111.
Many factors can influence the rate of HIV disease progression, including those that maintain T cell homeostasis. One key homeostatic regulator is the IL-7 receptor (IL-7R). Previous studies have shown IL-7R expression levels decrease in HIV infection, but effects on memory subtypes, CD4(+) T cells, and cell function have not been explored. The present study examined the expression of the IL-7Ralpha chain on naïve and memory T lymphocyte subsets of both HIV-positive and HIV-negative individuals from Nairobi, Kenya to assess the role of IL-7Ralpha in HIV disease. Expression of IL-7Ralpha was significantly reduced in all CD4(+) and CD8(+) T cell subsets in HIV-positive individuals. This reduction was further enhanced in those with advanced HIV progression. Expression of IL-7Ralpha was inversely correlated to immune activation, and apoptosis, and was positively correlated with CD4 count in both bivariate and multivariate analysis. Expression of IL-7Ralpha did not correlate with HIV viral loads, indicating the elevated immune activation seen in HIV-infected individuals may be impacting expression of IL-7Ralpha, independent of viral loads. Signaling via the IL-7R is essential for T cell homeostasis and maintenance of T cell memory. Reduction of this receptor may contribute to the homeostatic disruption seen in HIV.
许多因素可影响HIV疾病进展速度,包括那些维持T细胞稳态的因素。一个关键的稳态调节因子是白细胞介素-7受体(IL-7R)。先前的研究表明,HIV感染时IL-7R表达水平会降低,但对记忆亚群、CD4(+) T细胞及细胞功能的影响尚未探究。本研究检测了肯尼亚内罗毕HIV阳性和HIV阴性个体的初始和记忆T淋巴细胞亚群上IL-7Rα链的表达,以评估IL-7Rα在HIV疾病中的作用。HIV阳性个体所有CD4(+)和CD8(+) T细胞亚群中IL-7Rα的表达均显著降低。在HIV进展期患者中这种降低进一步加剧。在双变量和多变量分析中,IL-7Rα的表达与免疫激活及细胞凋亡呈负相关,与CD4计数呈正相关。IL-7Rα的表达与HIV病毒载量无关,这表明HIV感染个体中出现的免疫激活增强可能正在影响IL-7Rα的表达,与病毒载量无关。通过IL-7R的信号传导对于T细胞稳态及T细胞记忆的维持至关重要。该受体的减少可能导致HIV中出现的稳态破坏。