Lalvani A, Brookes R, Hambleton S, Britton W J, Hill A V, McMichael A J
Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
J Exp Med. 1997 Sep 15;186(6):859-65. doi: 10.1084/jem.186.6.859.
The nature of the CD8+ T cells that underlie antiviral protective immunological memory in vivo is unclear. We have characterized peptide-specific CD8+ T lymphocytes directly ex vivo from peripheral blood in humans with past exposure to influenza virus, using single cell interferon gamma (IFN-gamma) release as a measure of effector function. In individuals in the memory state with respect to influenza virus infection, unrestimulated antigen-specific CD8+ T cells displayed IFN-gamma release within 6 h of antigen contact, identifying a population of memory CD8+ T cells that exhibit effector function without needing to divide and differentiate over several days. We have quantified circulating CD8+ effector T cells specific for six different MHC class I-restricted influenza virus epitopes. Enumeration of these CD8+ T cells gives frequencies of peptide-specific T cells that correlate with, but are in general severalfold higher than, CTL precursor frequencies derived from limiting dilution analysis, indicating that this novel population of memory CD8+ T cells has hitherto been undetected by standard means. The phenotype of these cells, which persist at a low frequency long after recovery from an acute viral infection, suggests that they play a role in protective immunological memory.
体内抗病毒保护性免疫记忆所依赖的CD8 + T细胞的本质尚不清楚。我们利用单细胞干扰素γ（IFN-γ）释放作为效应器功能的衡量指标，直接从曾接触过流感病毒的人类外周血中对肽特异性CD8 + T淋巴细胞进行了离体鉴定。在处于流感病毒感染记忆状态的个体中，未受刺激的抗原特异性CD8 + T细胞在接触抗原后6小时内即释放IFN-γ，确定了一群无需经过数天的分裂和分化就能发挥效应器功能的记忆CD8 + T细胞。我们已对六种不同的MHC I类限制性流感病毒表位特异性的循环CD8 + 效应T细胞进行了定量。这些CD8 + T细胞的计数得出的肽特异性T细胞频率与通过有限稀释分析得出的CTL前体频率相关，但通常要高出几倍，这表明这种新型记忆CD8 + T细胞群体迄今尚未通过标准方法检测到。这些细胞在急性病毒感染恢复后很长时间仍以低频率持续存在，其表型表明它们在保护性免疫记忆中发挥作用。
