人类免疫缺陷病毒（HIV）对CD8 + T细胞CD57表达的影响不同于巨细胞病毒（CMV）和衰老的影响。

Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging.

作者信息

Lee Sulggi A, Sinclair Elizabeth, Hatano Hiroyu, Hsue Priscilla Y, Epling Lorrie, Hecht Frederick M, Bangsberg David R, Martin Jeffrey N, McCune Joseph M, Deeks Steven G, Hunt Peter W

机构信息

Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.

Department of Medicine, Massachusetts General Hospital and Harvard School of Public Health, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.

出版信息

PLoS One. 2014 Feb 27;9(2):e89444. doi: 10.1371/journal.pone.0089444. eCollection 2014.

DOI:10.1371/journal.pone.0089444

PMID:24586783

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3937334/

Abstract

BACKGROUND

Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase "immunosenesence" of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear.

METHODS

We compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV infection.

RESULTS

Compared to HIV-uninfected adults without CMV (n=12), those with asymptomatic CMV infection (n=31) had a higher proportion of CD28-CD8+ T cells expressing CD57 (P=0.005). Older age was also associated with greater proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P=0.007). In contrast, untreated HIV-infected CMV+ participants (n=55) had much lower proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+ participants (P<0.0001) and were enriched for less well-differentiated CD28- transitional memory (TTR) CD8+ T cells (P<0.0001). Chronically HIV-infected adults maintaining ART-mediated viral suppression (n=96) had higher proportions of CD28-CD8+ T cells expressing CD57 than untreated patients (P<0.0001), but continued to have significantly lower levels than HIV-uninfected controls (P=0.001). Among 45 HIV-infected individuals initiating their first ART regimen, the proportion of CD28-CD8+ T cells expressing CD57 declined (P<0.0001), which correlated with a decline in percent of transitional memory CD8+ T cells, and appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts rather than an expansion of CD28-CD57+ CD8+ T cell counts.

CONCLUSIONS

Unlike CMV and aging, which are associated with terminal differentiation and proliferation of effector memory CD8+ T cells, HIV inhibits this process, expanding less well-differentiated CD28- CD8+ T cells and decreasing the proportion of CD28- CD8+ T cells that express CD57.

摘要

背景

巨细胞病毒（CMV）的慢性抗原刺激被认为会增加衰老的“免疫衰老”，其特征是终末分化的CD28-CD8+T细胞积累以及增殖历史标志物CD57增加。慢性HIV感染是否会产生类似影响目前尚不清楚。

方法

我们比较了健康的未感染HIV的成年人（有或无CMV感染）以及未经治疗和接受抗逆转录病毒疗法（ART）抑制的无症状CMV感染的HIV感染成年人中CD8+T细胞分化标志物（如CD28、CD27、CCR7、CD45RA）和CD28-CD8+T细胞上CD57的表达。

结果

与未感染CMV的未感染HIV成年人（n = 12）相比，无症状CMV感染的成年人（n = 31）中表达CD57的CD28-CD8+T细胞比例更高（P = 0.005）。年龄较大也与表达CD57的CD28-CD8+T细胞比例更高相关（rho：0.47，P = 0.007）。相比之下，未经治疗的HIV感染的CMV+参与者（n = 55）中表达CD57的CD28-CD8+细胞比例远低于未感染HIV的CMV+参与者（P < 0.0001），并且富含分化程度较低的CD28-过渡性记忆（TTR）CD8+T细胞（P < 0.0001）。维持ART介导的病毒抑制的慢性HIV感染成年人（n = 96）中表达CD57的CD28-CD8+T细胞比例高于未经治疗的患者（P < 0.0001），但仍显著低于未感染HIV的对照组（P = 0.001）。在45名开始其首个ART方案的HIV感染个体中，表达CD57的CD28-CD8+T细胞比例下降（P < 0.0001），这与过渡性记忆CD8+T细胞百分比的下降相关，并且似乎主要由CD28-CD57-CD8+T细胞计数的下降而非CD28-CD57+CD8+T细胞计数的增加来解释。