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CD4+ T淋巴细胞上的白细胞介素-7受体α(IL-7Rα)表达随着HIV疾病进展而降低,且与免疫激活呈负相关。

IL-7Ralpha expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation.

作者信息

Koesters Sandra A, Alimonti Judie B, Wachihi Charles, Matu Lucy, Anzala Omu, Kimani Joshua, Embree Joanne E, Plummer Francis A, Fowke Keith R

机构信息

Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada, R3E 0 W3.

出版信息

Eur J Immunol. 2006 Feb;36(2):336-44. doi: 10.1002/eji.200535111.

Abstract

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.

摘要

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。

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