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在恒河猴原发性猴免疫缺陷病毒感染期间,细胞毒性T淋巴细胞(CTL)的出现与病毒清除同时发生。

Emergence of CTL coincides with clearance of virus during primary simian immunodeficiency virus infection in rhesus monkeys.

作者信息

Kuroda M J, Schmitz J E, Charini W A, Nickerson C E, Lifton M A, Lord C I, Forman M A, Letvin N L

机构信息

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

出版信息

J Immunol. 1999 May 1;162(9):5127-33.

Abstract

The CTL response was characterized during primary SIV/macaque (SIVmac) infection of rhesus monkeys to assess its role in containing early viral replication using both an epitope-specific functional and an MHC class I/peptide tetramer-binding assay. The rapid expansion of a single dominant viral epitope-specific CTL population to 1.3-8.3% of circulating CD8+ peripheral blood and 0. 3-1.3% of lymph node CD8+ T cells was observed, peaking at day 13 following infection. A subsequent decrease in number of these cells was then demonstrated. Interestingly, the percent of tetramer-binding CD8+ T cells detected in the lymph nodes of all evaluated animals was smaller than the percent detected in PBL. These epitope-specific CD8+ T cells expressed cell surface molecules associated with memory and activation. Early clearance of SIVmac occurred coincident with the emergence of the CTL response, suggesting that CTL may be important in containing virus replication. A higher percent of annexin V-binding cells was detected in the tetramer+ CD8+ T cells (range, from 33% to 75%) than in the remaining CD8+ T cells (range, from 3.3% to 15%) at the time of maximum CTL expansion in all evaluated animals. This finding indicates that the decrease of CTL occurred as a result of the death of these cells rather than their anatomic redistribution. These studies provide strong evidence for the importance of CTL in containing AIDS virus replication.

摘要

在恒河猴初次感染猴免疫缺陷病毒(SIVmac)期间,对细胞毒性T淋巴细胞(CTL)反应进行了表征,以评估其在控制早期病毒复制中的作用,采用了表位特异性功能分析和MHC I类/肽四聚体结合分析。观察到单一优势病毒表位特异性CTL群体迅速扩增至循环CD8 +外周血的1.3 - 8.3%和淋巴结CD8 + T细胞的0.3 - 1.3%,在感染后第13天达到峰值。随后证明这些细胞数量减少。有趣的是,在所有评估动物的淋巴结中检测到的四聚体结合CD8 + T细胞百分比低于在外周血淋巴细胞(PBL)中检测到的百分比。这些表位特异性CD8 + T细胞表达与记忆和激活相关的细胞表面分子。SIVmac的早期清除与CTL反应的出现同时发生,表明CTL可能在控制病毒复制中起重要作用。在所有评估动物的CTL最大扩增时,在四聚体+ CD8 + T细胞中检测到的膜联蛋白V结合细胞百分比(范围为33%至75%)高于其余CD8 + T细胞(范围为3.3%至15%)。这一发现表明CTL的减少是由于这些细胞的死亡而非其解剖学重新分布所致。这些研究为CTL在控制艾滋病病毒复制中的重要性提供了有力证据。

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