HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells
HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells
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DOI：
10.1182/blood-2005-12-4818
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发表时间：
2006-06-15
期刊：
影响因子：
20.3
通讯作者：
Koup, Richard A.
中科院分区：
文献类型：
--
作者：
Betts, Michael R.;Nason, Martha C.;Koup, Richard A.
建立CD 8（+）T细胞介导的免疫相关的HIV疾病的保护是至关重要的疫苗设计，以产生细胞介导的免疫的发展。从历史上看，HIV特异性CD 8（+）T细胞反应的数量和广度都与保护作用没有决定性的联系。在此，我们通过同时测量慢性HIV感染者和精英非进展者的5种CD 8（+）T细胞功能（脱颗粒、IFN-γ、MIP-1 β、TNF-α和IL-2）来评估HIV特异性CD 8（+）T细胞应答的质量。我们发现，HIV特异性CD 8（+）T细胞在进展者中的功能特征与非进展者相比是有限的，后者始终保持高功能的CD 8（+）T细胞。这种有限的功能是独立的HLA类型和T细胞记忆表型，是HIV特异性的，而不是普遍的，并没有有效地恢复治疗干预。尽管总HIV特异性CD 8（+）T细胞频率与病毒载量无关，但具有最高功能的HIV特异性T细胞应答的频率和比例与进展者的病毒载量呈负相关。因此，CD 8（+）T细胞功能性应答的质量不是数量或表型，而是HIV疾病进展的免疫相关因素，也是评价HIV疫苗疗效的潜在合格因素。
Establishing a CD8(+) T cell-mediated immune correlate of protection in HIV disease is crucial to the development of vaccines designed to generate cell-mediated immunity. Historically, neither the quantity nor breadth of the HIV-specific CD8(+) T-cell response has correlated conclusively with protection. Here, we assess the quality of the HIV-specific CD8(+) T-cell response by measuring 5 CD8(+) T-cell functions (degranulation, IFN-gamma, MIP-1 beta, TNF-alpha, and IL-2) simultaneously in chronically HIV-Infected individuals and elite nonprogressors. We find that the functional profile of HIV-specific CD8(+) T cells in progressors is limited compared to that of nonprogressors, who consistently maintain highly functional CD8(+) T cells. This limited functionality is independent of HLA type and T-cell memory phenotype, is HIV-specific rather than generalized, and is not effectively restored by therapeutic intervention. Whereas the total HIV-specific CD8(+) T-cell frequency did not correlate with viral load, the frequency and proportion of the HIV-specific T-cell response with highest functionality inversely correlated with viral load in the progressors. Thus, rather than quantity or phenotype, the quality of the CD8(+) T-cell functional response serves as an immune correlate of HIV disease progression and a potential qualifying factor for evaluation of HIV vaccine efficacy.