Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
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DOI：
10.1371/journal.ppat.1004345
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发表时间：
2014-08
期刊：
影响因子：
6.7
通讯作者：
Silvestri G
中科院分区：
文献类型：
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作者：
Klatt NR;Bosinger SE;Peck M;Richert-Spuhler LE;Heigele A;Gile JP;Patel N;Taaffe J;Julg B;Camerini D;Torti C;Martin JN;Deeks SG;Sinclair E;Hecht FM;Lederman MM;Paiardini M;Kirchhoff F;Brenchley JM;Hunt PW;Silvestri G
一种罕见的HIV感染者亚群，称为病毒血症无进展者（VNP），尽管持续高病毒血症，但仍保持无症状并维持正常的CD4 + T细胞水平。为了鉴定可能导致VNP表型的机制，我们将VNP（平均> 9年的HIV感染）与HIV感染个体进行比较，所述HIV感染个体具有相似的CD4 + T细胞计数和病毒载量，但如果不治疗则可能进展（"推定的进展者"，PP），从而避免了与大量CD4 + T细胞耗竭相关的差异的混杂效应。我们发现，与PP相比，VNPs保留了CD4+干细胞记忆细胞（TSCM）的水平（p <0.0001），这与VNPs中这些细胞的HIV感染减少有关（r =-0.649，p = 0.019）。 此外，VNPs降低了CD 4+中央记忆（TCM）细胞中的HIV感染（p = 0.035），TCM细胞总数与记忆CD 4 + T细胞增殖增加相关（r = 0.733，p = 0.01）。 我们的研究结果表明，在HIV感染的VNPs中，CD4 + TCM和TSCM的感染减少，细胞参与了CD4 + T细胞稳态的保持，尽管病毒血症很高，但缺乏疾病进展。在这里，我们评估了一个罕见的艾滋病毒感染者，病毒血症无进展者（VNP）的疾病进展保护的相关性。这些人有高病毒载量数年。然而，与大多数感染者相反，这些人不会发展成艾滋病。在这里，我们发现这种进展的缺乏与选择性保存记忆CD4 + T细胞的两个关键子集，中央记忆（TCM）和干细胞记忆（TSCM）细胞有关。与HIV感染的假定进展者相比，VNPs具有更高的这些不可或缺的记忆细胞亚群的增殖。此外，与不太重要的效应记忆CD4 + T细胞相比，VNP中的长寿命CD4 + TCM和TSCM细胞具有降低的HIV感染，这表明VNP在感染数年后维持其CD4 + T细胞库并保持免于AIDS进展的可能机制。
A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated (“putative progressors”, PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = −0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p = 0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia. Here we assessed correlates of protection from disease progression in a rare subset of HIV-infected individuals, viremic non-progressors (VNP). These individuals have high viral load for several years. In contrast to the majority of infected individuals, however, these individuals do not progress to AIDS. Here we found this lack of progression was associated with selective preservation of two critical subsets of memory CD4+ T cells, central memory (TCM) and stem-cell memory (TSCM) cells. Compared to HIV-infected putative progressors, VNPs had higher proliferation of these indispensable subsets of memory cells. In addition, the long-lived CD4+ TCM and TSCM cells in VNPs had decreased HIV infection compared to the less critical effector memory CD4+ T cells, which indicates a possible mechanism by which VNPs maintain their CD4+ T cell pool after several years of infection, and remain free from AIDS progression.
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DOI：
10.1097/qai.0b013e318269c414
发表时间：
2012-12-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Groves KC;Bibby DF;Clark DA;Isaksen A;Deayton JR;Anderson J;Orkin C;Stagg AJ;McKnight A
通讯作者：
McKnight A
影响因子：
2.8
作者：
Ballana, Ester;Ruiz-de Andres, Alba;Este, Jose A.
通讯作者：
Este, Jose A.
影响因子：
20.3
作者：
Klatt, Nichole R.;Vinton, Carol L.;Brenchley, Jason M.
通讯作者：
Brenchley, Jason M.
影响因子：
4.4
作者：
Elrefaei, M;McElroy, MD;Cao, HY
通讯作者：
Cao, HY
影响因子：
82.9
作者：
通讯作者：
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