Arizcorreta A, Márquez M, Fernández-Gutiérrez C, Guzmán E Pérez, Brun F, Rodríguez-Iglesias M, Girón-González J A
Servicios de Medicina Interna, Hospital Universitario Puerta del Mar, Cádiz, Spain.
Clin Exp Immunol. 2006 Nov;146(2):270-7. doi: 10.1111/j.1365-2249.2006.03220.x.
Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+) subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively. Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4(+) CD45RA(+) subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89 (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4(+) and CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV co-infected patients treated with pegIFN-alpha was observed. Both subpopulations increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation did not reach the basal levels as a consequence, at least in part, of a decrease in thymic production.
干扰素(IFN)-α诱导的CD4(+) T淋巴细胞减少是人类免疫缺陷病毒(HIV)合并感染的慢性丙型肝炎病毒(HCV)患者治疗中的一种毒性作用。为了增加对这种继发效应的了解,我们对聚乙二醇干扰素α(pegIFN-α)+利巴韦林治疗慢性丙型肝炎期间T细胞受体切除环(TRECs)、CD4(+)和CD8(+) T细胞及其CD45RO(+)和CD45RA(+)亚群的演变进行了分析。20例HIV/HCV合并感染患者,在高效抗逆转录病毒治疗(HAART)后HIV载量检测不到,接受pegIFN-α+利巴韦林治疗。使用实时聚合酶链反应测定TRECs。通过双色流式细胞术分析CD4(+)和CD8(+) T细胞及其CD45RO(+)和CD45RA(+)亚群。基线时CD4(+)和CD8(+) T细胞的中位数分别为592个/mm(3)和874个/mm(3)。CD4(+) T淋巴细胞的CD45RO(+)亚群基线中位数为48%,CD8(+) T淋巴细胞为57%。检测到两个T细胞群体及其CD45RO(+)和CD45RA(+)亚群均逐渐减少,基线水平与最低点水平之间的差异接近50%。T细胞群体和TRECs的演变与治疗反应无关。治疗结束后24周,T淋巴细胞及其亚群恢复到基线水平,但T CD4(+) CD45RA(+)亚群除外。CD4(+) CD45RO(+)/CD4(+) CD45RA(+)的比值从0.89(基线)增加到1.44(治疗结束后24周)。TRECs/ml未恢复到基础值。总之,观察到接受pegIFN-α治疗的HIV/HCV合并感染患者中,CD4(+)和CD8(+) T细胞及其CD45RA(+)和CD45RO(+)亚群显著减少。治疗停止后两个亚群均增加,但CD4(+) CD45RA亚群至少部分由于胸腺生成减少而未达到基础水平。