调节性 T 细胞与 AIDS 患者巨细胞病毒终末器官疾病的风险。
Regulatory T cells and the risk of CMV end-organ disease in patients with AIDS.
机构信息
*Department of Pediatric Medicine and Pathology, School of Medicine, University of Colorado Denver, Aurora, CO; †Department of Biostatistics, Harvard School of Public Health, Boston, MA; ‡Division of Infectious Diseases, School of Medicine, University of San Diego, San Diego, CA; §Division of Allergy and Infectious Diseases, School of Medicine, Harborview Medical Center and the University of Washington School of Medicine, Seattle, WA; ‖Department of Infectious Diseases, School of Medicine, University of Stanford, Stanford, CA; ¶Department of Medicine, Division of Infectious Diseases, Weill Medical College of Cornell University, New York, NY; #Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; **Department of Medicine, St. Luke's-Roosevelt Medical Center and Columbia University College of Physicians and Surgeons, New York, NY; ††Servicio de Medicina Interna, Hospital Asepeyo Coslada, Madrid, Spain; and ‡‡Department of Medicine, University of California, San Francisco, San Francisco, CA.
出版信息
J Acquir Immune Defic Syndr. 2014 May 1;66(1):25-32. doi: 10.1097/QAI.0000000000000095.
OBJECTIVES
Cytomegalovirus (CMV)-specific T-cell effectors (CMV-Teff) protect against CMV end-organ disease (EOD). In HIV-infected individuals, their numbers and function vary with CD4 cell numbers and HIV load. The role of regulatory T cells (Treg) in CMV-EOD has not been extensively studied. We investigated the contribution of Treg and Teff toward CMV-EOD in HIV-infected individuals independently of CD4 cell numbers and HIV load and controlling for CMV reactivations.
DESIGN
We matched 43 CMV-EOD cases to 93 controls without CMV-EOD, but with similar CD4 cell numbers and HIV plasma RNA. CMV reactivation was investigated by blood DNA polymerase chain reaction over 32 weeks preceding the CMV-EOD in cases and preceding the matching point in controls.
METHODS
CMV-Teff and Treg were characterized by the expression of interferon-γ (IFN-γ), interleukin 2, tumor necrosis factor α (TNFα), MIP1β, granzyme B (GrB), CD107a, TNFα, FOXP3, and CD25.
RESULTS
Sixty-five percent cases and 20% controls had CMV reactivations. In multivariate analyses that controlled for CMV reactivations, none of the CMV-Teff subsets correlated with protection, but high CMV-GrB enzyme-linked immunosorbent spot responses and CMV-specific CD4FOXP3+%, CD4TNFα+%, and CD8CD107a% were significant predictors of CMV-EOD.
CONCLUSIONS
Because both FOXP3 and GrB have been previously associated with Treg activity, we conclude that CMV-Treg may play an important role in the development of CMV-EOD in advanced HIV disease. We were not able to identify a CMV-Teff subset that could be used as a surrogate of protection against CMV-EOD in this highly immunocompromised population.
目的
巨细胞病毒（CMV）特异性 T 细胞效应物（CMV-Teff）可预防 CMV 靶器官疾病（CMV-EOD）。在 HIV 感染者中，其数量和功能随 CD4 细胞数量和 HIV 载量而变化。调节性 T 细胞（Treg）在 CMV-EOD 中的作用尚未得到广泛研究。我们研究了 Treg 和 Teff 在 HIV 感染者中对 CMV-EOD 的作用，独立于 CD4 细胞数量和 HIV 载量，并控制了 CMV 再激活。
设计
我们匹配了 43 例 CMV-EOD 病例和 93 例无 CMV-EOD 但具有相似 CD4 细胞数量和 HIV 血浆 RNA 的对照者。通过在病例中 CMV-EOD 前 32 周和对照者中匹配点前的血液 DNA 聚合酶链反应（PCR）检测 CMV 再激活。
方法
通过干扰素-γ（IFN-γ）、白细胞介素 2、肿瘤坏死因子 α（TNFα）、MIP1β、颗粒酶 B（GrB）、CD107a、TNFα、FOXP3 和 CD25 的表达来描述 CMV-Teff 和 Treg。
结果
65%的病例和 20%的对照者发生 CMV 再激活。在控制 CMV 再激活的多变量分析中，没有一个 CMV-Teff 亚群与保护相关，但高 CMV-GrB 酶联免疫斑点反应和 CMV 特异性 CD4FOXP3+%、CD4TNFα+%和 CD8CD107a%是 CMV-EOD 的显著预测因子。
结论
由于 FOXP3 和 GrB 以前都与 Treg 活性有关，我们得出结论，CMV-Treg 可能在 HIV 疾病晚期 CMV-EOD 的发展中发挥重要作用。在这个高度免疫受损的人群中，我们无法确定一个 CMV-Teff 亚群可以作为预防 CMV-EOD 的替代物。
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