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在接种疫苗且感染猿猴人类免疫缺陷病毒的恒河猴中功能性病毒特异性记忆CD8 + T淋巴细胞的保存

Preservation of functional virus-specific memory CD8+ T lymphocytes in vaccinated, simian human immunodeficiency virus-infected rhesus monkeys.

作者信息

Acierno Paula M, Schmitz Jörn E, Gorgone Darci A, Sun Yue, Santra Sampa, Seaman Michael S, Newberg Michael H, Mascola John R, Nabel Gary J, Panicali Dennis, Letvin Norman L

机构信息

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, USA.

出版信息

J Immunol. 2006 May 1;176(9):5338-45. doi: 10.4049/jimmunol.176.9.5338.

Abstract

Functional impairment of virus-specific memory CD8(+) T lymphocytes has been associated with clinical disease progression following HIV, SIV, and simian human immunodeficiency virus infection. These lymphocytes have a reduced capacity to produce antiviral cytokines and mediators involved in the lysis of virally infected cells. In the present study, we used polychromatic flow cytometry to assess the frequency and functional capacity of central memory (CD28(+)CD95(+)) and effector memory (CD28(-)CD95(+)) subpopulations of Gag-specific CD8(+) T cells in SIV/simian human immunodeficiency virus-infected rhesus monkeys. The aim of this study was to determine whether Ag-specific, memory CD8(+) T cell function could be preserved in infected monkeys that had been immunized before infection with a vaccine regimen consisting of a plasmid DNA prime followed by a recombinant viral vector boost. We observed that vaccination was associated with the preservation of Gag-specific central memory CD8(+) T cells that were functionally capable of producing IFN-gamma, and effector memory CD8(+) T cells that were capable of producing granzyme B following viral Ag exposure.

摘要

病毒特异性记忆性CD8(+) T淋巴细胞的功能损害与HIV、SIV和猿猴免疫缺陷病毒感染后的临床疾病进展相关。这些淋巴细胞产生抗病毒细胞因子和参与裂解病毒感染细胞的介质的能力降低。在本研究中,我们使用多色流式细胞术评估了SIV/猿猴免疫缺陷病毒感染的恒河猴中Gag特异性CD8(+) T细胞的中央记忆亚群(CD28(+)CD95(+))和效应记忆亚群(CD28(-)CD95(+))的频率和功能能力。本研究的目的是确定在感染前用由质粒DNA初免随后重组病毒载体加强的疫苗方案进行免疫的感染猴中,抗原特异性记忆性CD8(+) T细胞功能是否能够得以保留。我们观察到,疫苗接种与保留功能上能够产生IFN-γ的Gag特异性中央记忆CD8(+) T细胞以及在病毒抗原暴露后能够产生颗粒酶B的效应记忆CD8(+) T细胞相关。

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