Billerbeck Eva, Blum Hubert E, Thimme Robert
Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.
J Immunol. 2007 Jul 15;179(2):1039-48. doi: 10.4049/jimmunol.179.2.1039.
Although FoxP3 has been shown to be the most specific marker for regulatory CD4(+) T cells, its significance in the CD8(+) T cell population is not well understood. In this study, we show that the in vitro stimulation of human PBMC with hepatitis C virus or Flu virus-specific peptides gives rise to two distinct Ag-specific T cell populations: FoxP3(-) and FoxP3(+)CD8(+) T cells. The FoxP3(+) virus-specific CD8(+) T cells share phenotypical markers of regulatory T cells, such as CTLA-4 and glucocorticoid-induced TNFR family-related gene, and do produce moderate amounts of IFN-gamma but not IL-2 or IL-10. IL-2 and IL-10 are critical cytokines, however, because the expansion of virus-specific FoxP3(+)CD8(+) T cells is blocked by IL-2- or IL-10-neutralizing mAbs. The virus-specific FoxP3(+)CD8(+) T cells have a reduced proliferative capacity, indicating anergy, and display a cell-cell contact-dependent suppressive activity. Taken together, our results indicate that stimulation with a defined viral Ag leads to the expansion of two different cell populations: FoxP3(-) memory/effector as well as FoxP3(+) regulatory virus-specific CD8(+) T cells.
尽管FoxP3已被证明是调节性CD4(+) T细胞最特异的标志物，但其在CD8(+) T细胞群体中的意义尚未得到充分了解。在本研究中，我们发现用丙型肝炎病毒或流感病毒特异性肽体外刺激人外周血单核细胞（PBMC）可产生两种不同的抗原特异性T细胞群体：FoxP3(-)和FoxP3(+) CD8(+) T细胞。FoxP3(+)病毒特异性CD8(+) T细胞具有调节性T细胞的表型标志物，如CTLA-4和糖皮质激素诱导的肿瘤坏死因子受体家族相关基因，并且确实产生适量的干扰素-γ，但不产生白细胞介素-2或白细胞介素-10。然而，白细胞介素-2和白细胞介素-10是关键细胞因子，因为病毒特异性FoxP3(+) CD8(+) T细胞的扩增被白细胞介素-2或白细胞介素-10中和单克隆抗体所阻断。病毒特异性FoxP3(+) CD8(+) T细胞的增殖能力降低，表明其处于无反应状态，并表现出细胞间接触依赖性抑制活性。综上所述，我们的结果表明，用特定病毒抗原刺激可导致两种不同细胞群体的扩增：FoxP3(-)记忆/效应细胞以及FoxP3(+)调节性病毒特异性CD8(+) T细胞。
