Immune Responses Driven by Protective Human Leukocyte Antigen Alleles From Long-term Nonprogressors Are Associated With Low HIV Reservoir in Central Memory CD4 T Cells
Immune Responses Driven by Protective Human Leukocyte Antigen Alleles From Long-term Nonprogressors Are Associated With Low HIV Reservoir in Central Memory CD4 T Cells
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DOI：
10.1093/cid/cis188
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发表时间：
2012-05-15
影响因子：
11.8
通讯作者：
Autran, Brigitte
中科院分区：
文献类型：
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作者：
Descours, Benjamin;Avettand-Fenoel, Veronique;Autran, Brigitte
背景人类免疫缺陷病毒（HIV）在具有保护性人类白细胞抗原（HLA）等位基因的长期非进展者（LTNP）中的稳定免疫控制提出了这些等位基因是否以及如何影响HIV患者的免疫分布的问题。对8名携带和10名不携带HLA-B（星星）27或HLA-B（星星）57等位基因（HLA-B27/B57）的LTNP的血液分选的静息CD 4 T细胞亚群中的细胞相关HIV-DNA水平进行定量。中枢记忆性CD 4 T细胞（T-CM）感染水平显著降低是区分HLA-B27/B57 HIV储库与其他储库的唯一特征。在LTNP中，T-CM保护与T-CM计数的保存相关，T-CM计数与HIV Gag特异性CD 8 T细胞的数量呈正相关。在HLA-B27/B57 LTNP中，其记忆性CD 4 T细胞的较低活化水平与每个静息记忆性CD 4亚群中细胞HIV-DNA的量较低相关，并且还与HIV Gag特异性CD 8 T细胞/感染的静息CD 4 T细胞的较高比率相关（效应/靶[E/T]）。结果显示，HLA-B27/B57 E/T比值与记忆性CD 4 T细胞亚群在HIV感染者中的比例呈负相关。由保护性HLA-B27/B57等位基因通过限制T-CM感染和库耗尽控制的有效抗病毒免疫与减少T-CM对HIV储库的贡献相关。
Background. The stable immune control of human immunodeficiency virus (HIV) in long-term nonprogressors (LTNPs) with protective human leukocyte antigen (HLA) alleles raises the question of whether and how these alleles influence the immune distribution of the HIV reservoirs.Methods. Cell-associated HIV-DNA levels were quantified in blood sorted resting CD4 T-cell subsets from 8 LTNPs with and 10 without HLA-B(star)27 or HLA-B(star)57 alleles (HLA-B27/B57).Results. A remarkably lower infection level of central memory CD4 T cells (T-CM) was an exclusive feature that distinguished the HLA-B27/B57 HIV reservoirs from the other ones. In LTNPs, T-CM protection was correlated with preservation of T-CM counts, which correlated positively with the magnitude of HIV Gag-specific CD8 T cells. In HLA-B27/B57 LTNPs, a lower activation level of their memory CD4 T cells was associated with lower amounts of cell HIV-DNA in each resting memory CD4 subset and were also associated with higher ratios of HIV Gag-specific CD8 T cells per infected resting CD4 T cell (effector/target [E/T]). As a result, HLA-B27/B57 E/T ratios were negatively correlated with the contribution of memory CD4 T-cell subsets to the total HIV reservoirs.Conclusions. The potent antiviral immunity governed by the protective HLA-B27/B57 alleles, by limiting T-CM infection and pool exhaustion, are associated with a reduced T-CM contribution to the HIV reservoir.