Dissociated production of perforin, granzyme B, and IFN-γ by HIV-specific CD8+ cells in HIV infection
Dissociated production of perforin, granzyme B, and IFN-γ by HIV-specific CD8+ cells in HIV infection
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DOI：
10.1089/aid.2007.0125
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发表时间：
2008-01-01
影响因子：
1.5
通讯作者：
Tary-Lehmann, Magdalena
中科院分区：
文献类型：
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作者：
Kuerten, Stefanie;Nowacki, Tobias M.;Tary-Lehmann, Magdalena
CD 8（+）T细胞在控制病毒感染（如HIV）方面起着至关重要的作用。HIV特异性CD 8（+）T细胞的功能特征迄今为止主要限于IFN-γ的研究。然而，TCR触发的效应分子穿孔素（PFN）和颗粒酶B（Gz B）的释放被认为是CD 8（+）效应T细胞破坏病毒感染的靶细胞的中心途径。在此，我们想谈谈两个主要的调查结果。一方面，我们提出，通过ELISPOT离体测量PFN和GzB分泌可能允许在健康和HIV感染个体中区分体内静息与活化的CD 8（+）记忆T细胞。因此，将目前IFN-γ测量的标准扩展到功能性T细胞测定中PFN和GzB释放的分析将为CD 8（+）效应T细胞功能提供新的见解。它应该能够通过其将IFN-γ阳性但GzB和PFN阴性的记忆性CD 8（+）T细胞重新激活和转化为PFN/GzB分泌效应细胞的能力来评估治疗性疫苗接种的功效。另一方面，我们报告了在慢性HIV感染中HIV肽诱导的PFN和GzB分泌的频繁离体解离，强调了这种疾病中CD 8（+）效应T细胞的多样性，这也是免疫监测方法中必须考虑的一个方面。
CD8(+) T cells play a crucial role in the control of viral infections such as HIV. The functional characterization of HIV-specific CD8(+) T cells has so far been largely restricted to studies of IFN-gamma. The TCR-triggered release of the effector molecules perforin (PFN) and granzyme B (GzB), however, is thought to be a central pathway for the destruction of virus-infected target cells by CD8(+) effector T cells. Here we would like to address two major findings. On the one hand we propose that ex vivo measurements of PFN and GzB secretion via ELISPOT may permit the distinction between in vivo resting versus activated CD8(+) memory T cells in healthy and HIV-infected individuals. Therefore, extending the present standard of IFN-gamma measurements to the analysis of PFN and GzB release in functional T cell assays will provide new insights into CD8(+) effector T cell functions. It should enable the evaluation of therapeutic vaccination efficacy by its ability to reactivate and convert IFN-gamma-positive, but GzB-and PFN-negative memory CD8(+) T cells into PFN/GzB-secreting effector cells. On the other hand, we report on a frequent ex vivo dissociation of the HIV peptide-induced secretion of PFN and GzB in chronic HIV infection underlining CD8(+) effector T cell diversity in this disease-an aspect that also has to be accounted for in immune monitoring approaches.