Lucas Michaela, Vargas-Cuero Ana L, Lauer Georg M, Barnes Eleanor, Willberg Christian B, Semmo Nasser, Walker Bruce D, Phillips Rodney, Klenerman Paul
Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
J Immunol. 2004 Feb 1;172(3):1744-53. doi: 10.4049/jimmunol.172.3.1744.
Recent studies using MHC class I tetramers have shown that CD8(+) T cell responses against different persistent viruses vary considerably in magnitude and phenotype. At one extreme, hepatitis C virus (HCV)-specific CD8(+) T cell responses in blood are generally weak and have a phenotype that is perforin low and CCR7 high (early memory). At the other, specific responses to CMV are strong, perforin high, and CCR7 low (mature or effector memory). To examine the potential mechanisms behind this diversity, we compared CMV-specific responses in HCV-infected and healthy individuals. We find a striking difference in the phenotype of CMV-specific CD8(+) T cells between these groups. In the HCV-infected cohort, CMV-specific CD8(+) T cells lost markers associated with maturity; they had increased expression of CCR7 and reduced expression of Fas and perforin. They nevertheless responded to Ag in vitro in a manner similar to controls, with strong proliferation and appropriate acquisition of effector memory markers. The reduction in mature CD8 T cells in HCV-infected individuals may arise through either impairment or regulation of T cell stimulation, or through the early loss of mature T cells. Whatever the mechanism, HCV has a pervasive influence on the circulating CD8(+) T cell population, a novel feature that may be a hallmark of this infection.
最近使用MHC I类四聚体的研究表明，针对不同持续性病毒的CD8(+) T细胞反应在强度和表型上有很大差异。在一个极端情况下，血液中丙型肝炎病毒（HCV）特异性CD8(+) T细胞反应通常较弱，具有穿孔素低、CCR7高的表型（早期记忆）。在另一个极端，对巨细胞病毒（CMV）的特异性反应很强，穿孔素高，CCR7低（成熟或效应记忆）。为了研究这种多样性背后的潜在机制，我们比较了HCV感染个体和健康个体中针对CMV的反应。我们发现这两组之间CMV特异性CD8(+) T细胞的表型存在显著差异。在HCV感染队列中，CMV特异性CD8(+) T细胞失去了与成熟相关的标志物；它们的CCR7表达增加，Fas和穿孔素表达降低。然而，它们在体外对抗原的反应方式与对照组相似，具有强烈的增殖和效应记忆标志物的适当获得。HCV感染个体中成熟CD8 T细胞的减少可能是由于T细胞刺激的受损或调节，或者是由于成熟T细胞的早期丢失。无论机制如何，HCV对循环CD8(+) T细胞群体有广泛影响，这一新颖特征可能是这种感染的一个标志。
