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首页> 外文期刊>AIDS Research and Human Retroviruses >Dissociated Production of Perforin, Granzyme B, and IFN-γ by HIV-Specific CD8+ Cells in HIV Infection
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Dissociated Production of Perforin, Granzyme B, and IFN-γ by HIV-Specific CD8+ Cells in HIV Infection

机译：HIV特异性CD8 +细胞在HIV感染中解离产生穿孔素，颗粒酶B和IFN-γ

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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-γ. 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-γ 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-γ-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.
机译：CD8 + T细胞在控制HIV等病毒感染中起着至关重要的作用。迄今为止，HIV特异性CD8 + T细胞的功能表征在很大程度上局限于IFN-γ的研究。 TCR触发效应分子穿孔素（PFN）和粒酶B（GzB）的释放被认为是CD8 +效应T细胞破坏病毒感染靶细胞的主要途径。在这里，我们想谈谈两个主要发现。一方面，我们提出通过离体测量通过ELISPOT对PFN和GzB的分泌，可以区分健康人和HIV感染者体内的静息与活化的CD8 +记忆T细胞。因此，将目前的IFN-γ测量标准扩展到功能性T细胞测定中PFN和GzB释放的分析将为CD8 +效应子T细胞功能提供新的见解。它应该能够通过其重新激活IFN-γ阳性但GzB和PFN阴性记忆的CD8 + T细胞并将其转化为分泌PFN / GzB的效应细胞并将其转化的能力来评估治疗疫苗的效力。另一方面，我们报道了在慢性HIV感染中HIV肽诱导的PFN和GzB分泌的频繁离体解离，突显了该疾病中CD8 +效应T细胞的多样性–这也是免疫中必须考虑的一个方面监控方法。

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