抗逆转录病毒治疗后病毒学抑制的 HIV 感染患者中，CD8 T 细胞激活与脂肪营养不良和内脏脂肪堆积有关。

CD8 T-cell activation is associated with lipodystrophy and visceral fat accumulation in antiretroviral therapy-treated virologically suppressed HIV-infected patients.

机构信息

*Department of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy; †Department of Medicine, Surgery and Dentistry, Clinic of Infectious and Tropical Diseases, University of Milano, Milan, Italy; ‡Serviço de Doenças Infecciosas, Hospital de Joaquim Urbano, Porto, Portugal; and §Biochimie et Hormonologie, Hôpital Tenon AP-HP Paris, CDR Saint-Antoine, Inserm U938, Université Paris6-UPMC, Faculté de Médecine Pierre et Marie Curie, Paris, France.

出版信息

J Acquir Immune Defic Syndr. 2013 Dec 1;64(4):360-6. doi: 10.1097/QAI.0000000000000001.

DOI:10.1097/QAI.0000000000000001

PMID:24129368

Abstract

OBJECTIVE

HIV-infected patients receiving antiretroviral treatment frequently accumulate fat at the abdominal level. It is unknown whether T-cell activation and immune phenotypes are associated with fat accumulation. Thus, the aim of the study was to search for an association between the presence of clinical lipodystrophy (LD), visceral and subcutaneous abdominal adipose tissue amount (VAT and SAT), and peripheral T-cell immune phenotypes.

DESIGN

Cross-sectional study including 87 HIV-infected antiretroviral therapy-treated virologically suppressed and immune-reconstituted patients.

METHODS

The patients were evaluated for clinical LD, VAT, SAT, homeostasis model of insulin resistance, and coronary artery calcium score (>10). T-cell activation (CD8/CD38), differentiation (CD4/CD8/CCR7/CD45RA), and expression/activation of the interleukin-7 (IL-7)/IL-7R system (CD4/CD8/CD127, IL-7, and CD4/CD8/pStat-5) were assessed by cytometry.

RESULTS

In multivariable analyses, CD8 T-cell activation (CD38) was associated with lipoatrophy and central fat accumulation (respectively, β = 5.63, P = 0.005, and β = 4.19, P = 0.020). This was also the case for IL-7R expressing CD8⁺ T cells (CD127⁺) for lipoatrophy β = 12.8, P = 0.003, and for central fat accumulation β = 9.45, P = 0.016. CD8⁺ T-cell activation was also associated with VAT/total adipose tissue (β = 0.01, P = 0.002) and SAT/VAT ratios (β = -0.014, P = 0.015). As expected, VAT/total adipose tissue was an independent risk factor for homeostasis model of insulin resistance (r = 0.364, P = 0.028) and cardiovascular risk (coronary artery calcium, r = 0.406, P = 0.002).

CONCLUSIONS

CD8⁺ T-cell activation was associated with LD and the relative amount of VAT in antiretroviral therapy-controlled, virologically suppressed, HIV-infected patients. We propose that CD8 activation may be involved in the accumulation of central fat frequently observed in these patients, with resulting increased cardiometabolic risk.

摘要

目的

接受抗逆转录病毒治疗的 HIV 感染患者常出现腹部脂肪堆积。目前尚不清楚 T 细胞激活和免疫表型是否与脂肪堆积有关。因此，本研究旨在探讨临床脂代谢障碍（LD）、内脏和皮下腹部脂肪量（VAT 和 SAT）与外周 T 细胞免疫表型之间的关系。

设计

包括 87 例接受抗逆转录病毒治疗的病毒抑制和免疫重建的 HIV 感染患者的横断面研究。

方法

评估患者的临床 LD、VAT、SAT、胰岛素抵抗的稳态模型评估（HOMA-IR）和冠状动脉钙评分（>10）。通过流式细胞术评估 T 细胞激活（CD8/CD38）、分化（CD4/CD8/CCR7/CD45RA）和白细胞介素 7（IL-7）/IL-7 受体系统（CD4/CD8/CD127、IL-7、CD4/CD8/pStat-5）的表达/激活。

结果

多变量分析显示，CD8 T 细胞激活（CD38）与脂肪减少和中心性脂肪堆积有关（分别为β=5.63，P=0.005 和β=4.19，P=0.020）。IL-7R 表达的 CD8+T 细胞（CD127+）也与脂肪减少有关（β=12.8，P=0.003），与中心性脂肪堆积有关（β=9.45，P=0.016）。CD8+T 细胞激活与 VAT/总脂肪组织（β=0.01，P=0.002）和 SAT/VAT 比值（β=-0.014，P=0.015）也有关。如预期的那样，VAT/总脂肪组织是胰岛素抵抗的稳态模型（r=0.364，P=0.028）和心血管风险（冠状动脉钙，r=0.406，P=0.002）的独立危险因素。