Background

HIV-associated immunodeficiency is related to loss of CD4⁺ T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4⁺ T cells/μL. CD8⁺CD28⁻CD127^loCD39⁺ T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients.

Objectives

We sought to analyze the frequency of CD8⁺CD28⁻CD127^loCD39⁺ Treg cells in the circulation of HIV-infected patients.

Methods

The frequency of circulating CD8⁺CD28⁻CD127^loCD39⁺ Treg cells was analyzed and correlated with viral load and CD4⁺ T-cell counts/percentages in 93 HIV-1–infected patients subdivided as follows: naive (n = 63), elite controllers (n = 19), long-term nonprogressors (n = 7), and HIV-infected patients affected by tumor (n = 4). The same analyses were performed in HIV-negative patients with cancer (n = 53), hepatitis C virus–infected patients (n = 17), and healthy donors (n = 173).

Results

HIV-infected patients had increased circulating levels of functional CD8⁺CD28⁻CD127^loCD39⁺ Treg cells. These cells showed antigen specificity against HIV proteins. Their frequency after antiretroviral therapy (ART) correlated with HIV viremia, CD4⁺ T-cell counts, and immune activation markers, suggesting their pathogenic involvement in AIDS- or non–AIDS-related complications. Their increase after initiation of ART heralded a lack of virologic or clinical response, and hence their monitoring is clinically relevant.

Conclusion

HIV infection induces remarkable expansion of CD8⁺CD28⁻CD127^loCD39⁺ Treg cells, the frequency of which correlates with both clinical disease and signs of chronic immune cell activation. Monitoring their frequency in the circulation is a new marker of response to ART when effects on viremia and clinical response are not met.

中文翻译：

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CD8 ⁺ CD28 ^- CD127 ^LO CD39 ⁺调节性T细胞扩增：一种新的可能的致病机制HIV感染？

背景

HIV相关的免疫缺陷与CD4 ⁺ T细胞的丢失有关。这种机制不能解释HIV疾病的某些表现，例如CD4 ⁺ T细胞/μL大于500的患者的免疫缺陷事件。CD8 ⁺ CD28 ^- CD127 ^LO CD39 ⁺ T细胞是高度集中在肿瘤微环境中和HIV感染患者的循环从不分析调节性T（Treg）淋巴细胞。

目标

我们试图分析CD8频率⁺ CD28 ^- CD127 ^LO CD39 ⁺ Treg细胞在艾滋病毒感染者的血液循环。

方法

对93名HIV-1感染患者的循环CD8 ⁺ CD28 ^- CD127 ^lo CD39 ⁺ Treg细胞频率进行了分析，并将其与病毒载量和CD4 ⁺ T细胞计数/百分数相关，分为以下几类：幼稚（n = 63），精英控制者（n = 19），长期非进展者（n = 7）和受肿瘤影响的HIV感染患者（n = 4）。在HIV阴性的癌症患者（n = 53），丙型肝炎病毒感染的患者（n = 17）和健康的捐献者（n = 173）中进行了相同的分析。

结果

艾滋病毒感染者增加了功能性CD8的循环水平⁺ CD28 ^- CD127 ^LO CD39 ⁺ Treg细胞。这些细胞显示出针对HIV蛋白的抗原特异性。抗逆转录病毒疗法（ART）后，它们的发生频率与HIV病毒血症，CD4 ⁺ T细胞计数和免疫激活标志物相关，表明它们的病原体参与了与AIDS或非AIDS相关的并发症。接受抗逆转录病毒治疗后它们的增加预示着缺乏病毒学或临床反应，因此其监测在临床上是相关的。

结论

HIV感染诱导CD8的明显扩张⁺ CD28 ^- CD127 ^LO CD39 ⁺ Treg细胞，其频率与两个临床疾病相关因素和慢性免疫细胞活化的标志。当未达到对病毒血症和临床反应的影响时，监测其循环频率是对ART反应的新标志。