Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity
Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity
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DOI：
10.1182/blood-2009-02-206557
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发表时间：
2009-06-18
期刊：
影响因子：
20.3
通讯作者：
Appay, Victor
中科院分区：
文献类型：
--
作者：
Almeida, Jorge R.;Sauce, Delphine;Appay, Victor
CD8(+) T细胞是抗HIV免疫反应的主要参与者。然而，最近基于T细胞的HIV-1疫苗开发的失败强调了需要重新评估我们对T细胞介导的功效的基本知识。来自疾病进展缓慢的hiv -1感染患者的CD8(+) T细胞表现出强大的多功能性和hiv抑制活性，然而统一这些特性的因素尚不完全清楚。我们使用体外分离的hiv特异性CD8(+) t细胞克隆库对t细胞功能属性之间的相互作用进行了详细的研究；这种方法使我们能够克服与体内t细胞群异质性相关的固有困难，并解决合成抗病毒功效所需品质的潜在决定因素。来自受感染供体的hiv特异性CD8(+) T细胞的离体分析支持了这一结论。我们报道CD8(+) t细胞抗HIV功效的属性与抗原敏感性水平有关。高度敏感的CD8(+) T细胞显示出多功能特征和有效的hiv抑制活性。这些数据为CD8(+) T细胞抗HIV有效性的机制提供了新的见解，并表明疫苗策略应侧重于诱导具有高水平抗原敏感性的HIV特异性T细胞，以获得有效的抗病毒效果。（血液。2009;113:6351-6360）
CD8(+) T cells are major players in the immune response against HIV. However, recent failures in the development of T cell-based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell-mediated efficacy. CD8(+) T cells from HIV-1-infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8(+) T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8(+) T cells from infected donors. We report that attributes of CD8(+) T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8(+) T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8(+) T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy. (Blood. 2009; 113: 6351-6360)