INSERM, Unite U955, Creteil, France.
J Acquir Immune Defic Syndr. 2012 Sep 1;61(1):56-63. doi: 10.1097/QAI.0b013e3182615b62.
The role of the thymus in the depletion or restoration of T-cell pool in HIV infection is still debatable. Studies are hampered by the lack of valuable tools to investigate thymic activity.
We have evaluated thymic activity using (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography and molecular and phenotypic analyses of thymic precursors. Longitudinal analyses were performed in HIV-infected patients either treatment naive with indication to initiate combination antiretroviral therapy (c-ART) (n = 11) or stable under c-ART (n = 9).
Thymic standardized uptake value was significantly lower in c-ART-treated patients as compared with historical age-matched HIV-negative controls. In c-ART-naive patients, baseline thymic standardized uptake value correlated with T-cell repector excision circle levels and naive CD4+ T cells. These patients exhibited a high metabolic lymph node activity positively correlated to the percentage of activated HLA-DR+CD38+ T cells. Basal metabolic thymic activity predicts the gain in CD4+ T cells after c-ART initiation. A decrease of thymic activity, which paralleled circulating plasma IL-7 levels, was noted after c-ART initiation.
A metabolic thymic activity is detectable in c-ART naive and correlates with indirect phenotypic and molecular markers of thymic output. This activity may participate to the pool of peripheral naive CD4+ T cells and predicts the magnitude of T-cell reconstitution under treatment.
胸腺在 HIV 感染中 T 细胞库耗竭或恢复中的作用仍存在争议。由于缺乏有价值的工具来研究胸腺活性,研究受到了阻碍。
我们使用(18)F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描以及胸腺前体细胞的分子和表型分析来评估胸腺活性。对有接受联合抗逆转录病毒治疗(c-ART)指征的 HIV 感染患者(治疗初治组,n=11)或正在接受 c-ART 治疗且病情稳定的患者(c-ART 治疗组,n=9)进行了纵向分析。
与历史匹配的 HIV 阴性对照组相比,c-ART 治疗组患者的胸腺标准化摄取值显著降低。在 c-ART 初治患者中,基线胸腺标准化摄取值与 T 细胞受体切除环水平和幼稚 CD4+T 细胞相关。这些患者表现出高代谢性淋巴结活性,与活化的 HLA-DR+CD38+T 细胞的百分比呈正相关。基础代谢性胸腺活性可预测 c-ART 启动后 CD4+T 细胞的增加。c-ART 启动后,胸腺活性下降,与循环血浆 IL-7 水平平行。
c-ART 初治患者中可检测到代谢性胸腺活性,且与间接的胸腺输出表型和分子标志物相关。这种活性可能参与外周幼稚 CD4+T 细胞池,并预测治疗下 T 细胞重建的程度。