Evolution of epitope-specific memory CD4+ T cells after clearance of hepatitis C virus

Evolution of epitope-specific memory CD4+ T cells after clearance of hepatitis C virus
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DOI:
10.4049/jimmunol.169.4.2210
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发表时间:
2002-08-15
影响因子:
4.4
通讯作者:
Openshaw, PJ
Openshaw, PJ
中科院分区:
医学2区
文献类型:
--
作者:
Godkin, AJ;Thomas, HC;Openshaw, PJ

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记忆淋巴细胞的产生是特异性免疫应答的标志之一。CD 4(+)T细胞应答在清除许多感染后维持长期保护性免疫方面至关重要。然而,这些记忆性CD 4(+)T细胞的准确表征主要依赖于小鼠研究,在人类中知之甚少。我们检测并计数了清除丙型肝炎病毒的患者中CD 4(+)记忆细胞的表位特异性群体。回忆反应的动力学和趋化因子受体CCR 7的表达表明存在不同的人群。在离体IFN-γ ELISPOT测定中测量的记忆细胞群体在病毒清除后稳定下降。然而,记忆性CD 4(+)T细胞仅在与Ag和IL-2短期培养后才具有特征,并且识别相同的表位,发育成长期稳定的群体。从PBMC中去除CCR 7(+)细胞显著降低了培养阳性群体中的反应,而对离体反应几乎没有影响。这些关键记忆子集在人类中的展示为定义它们在保护性免疫反应中的作用开辟了道路。
The generation of memory lymphocytes is one of the hallmarks of the specific immune response. The CD4(+) T cell response is of critical importance in maintaining long-term protective immunity after clearing many infections. However, accurate characterization of these memory CD4(+) T cells has relied mainly on mouse studies and is poorly understood in humans. We have detected and counted epitope-specific populations of CD4(+) memory cells in patients who have cleared hepatitis C virus. The kinetics of the recall response and the expression of the chemokine receptor CCR7 suggested the presence of distinct populations. A population of memory cells measured in an ex vivo IFN-gamma ELISPOT assay steadily declined after viral clearance. However, memory CD4(+) T cells only characterized after short-term culture with Ag and IL-2, and, recognizing the same epitopes, developed into a long-term stable population. Depletion of CCR7(+) cells from PBMCs markedly reduced the responses in the culture-positive population while having little effect on the ex vivo responses. The demonstration of these key memory subsets in man opens the way to defining their role in protective immune responses.