Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Azienda Ospedaliero Universitaria San Martino, IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Infectious Diseases Department, Sanremo Hospital, Imperia, Italy.
J Allergy Clin Immunol. 2018 Jun;141(6):2220-2233.e4. doi: 10.1016/j.jaci.2017.08.021. Epub 2017 Nov 2.
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. CD8CD28CD127CD39 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.
We sought to analyze the frequency of CD8CD28CD127CD39 Treg cells in the circulation of HIV-infected patients.
The frequency of circulating CD8CD28CD127CD39 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).
HIV-infected patients had increased circulating levels of functional CD8CD28CD127CD39 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.
HIV infection induces remarkable expansion of CD8CD28CD127CD39 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.
HIV 相关的免疫缺陷与 CD4 T 细胞的损失有关。这种机制并不能解释 HIV 疾病的某些表现，例如 CD4 T 细胞大于 500/μL 的患者的免疫缺陷事件。CD8CD28CD127CD39 T 细胞是调节性 T（Treg）淋巴细胞，它们高度集中在肿瘤微环境中，从未在 HIV 感染患者的循环中进行分析。
我们试图分析 HIV 感染患者循环中 CD8CD28CD127CD39 Treg 细胞的频率。
分析了 93 例 HIV-1 感染患者循环中 CD8CD28CD127CD39 Treg 细胞的频率，并与病毒载量和 CD4 T 细胞计数/百分比相关，这些患者分为以下几类：初治（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）。还对 HIV 阴性癌症患者（n=53）、丙型肝炎病毒感染患者（n=17）和健康供体（n=173）进行了相同的分析。
HIV 感染患者循环中功能性 CD8CD28CD127CD39 Treg 细胞水平升高。这些细胞对 HIV 蛋白具有抗原特异性。它们在抗逆转录病毒治疗（ART）后的频率与 HIV 病毒血症、CD4 T 细胞计数和免疫激活标志物相关，表明它们在 AIDS 或非 AIDS 相关并发症中具有致病性。ART 起始后它们的增加预示着缺乏病毒学或临床反应，因此监测它们具有临床意义。
HIV 感染诱导 CD8CD28CD127CD39 Treg 细胞的显著扩增，其频率与临床疾病和慢性免疫细胞激活标志物相关。监测其在循环中的频率是一种新的 ART 反应标志物，当对病毒血症和临床反应没有影响时。
