Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, UK.
Nat Med. 2013 Oct;19(10):1305-12. doi: 10.1038/nm.3350. Epub 2013 Sep 22.
The role of T cells in mediating heterosubtypic protection against natural influenza illness in humans is uncertain. The 2009 H1N1 pandemic (pH1N1) provided a unique natural experiment to determine whether crossreactive cellular immunity limits symptomatic illness in antibody-naive individuals. We followed 342 healthy adults through the UK pandemic waves and correlated the responses of pre-existing T cells to the pH1N1 virus and conserved core protein epitopes with clinical outcomes after incident pH1N1 infection. Higher frequencies of pre-existing T cells to conserved CD8 epitopes were found in individuals who developed less severe illness, with total symptom score having the strongest inverse correlation with the frequency of interferon-γ (IFN-γ)(+) interleukin-2 (IL-2)(-) CD8(+) T cells (r = -0.6, P = 0.004). Within this functional CD8(+)IFN-γ(+)IL-2(-) population, cells with the CD45RA(+) chemokine (C-C) receptor 7 (CCR7)(-) phenotype inversely correlated with symptom score and had lung-homing and cytotoxic potential. In the absence of crossreactive neutralizing antibodies, CD8(+) T cells specific to conserved viral epitopes correlated with crossprotection against symptomatic influenza. This protective immune correlate could guide universal influenza vaccine development.
T 细胞在介导针对人类自然流感疾病的异亚型保护中的作用尚不确定。2009 年 H1N1 大流行（pH1N1）提供了一个独特的自然实验，以确定交叉反应性细胞免疫是否限制了无抗体个体的症状性疾病。我们通过英国大流行波跟踪了 342 名健康成年人，并将对 pH1N1 病毒和保守核心蛋白表位的预先存在的 T 细胞反应与 pH1N1 感染后的临床结果相关联。在发生 pH1N1 感染后病情较轻的个体中，发现预先存在的 T 细胞对保守 CD8 表位的频率更高，总症状评分与干扰素-γ（IFN-γ）（+）白细胞介素-2（IL-2）（-）CD8（+）T 细胞频率呈最强负相关（r = -0.6，P = 0.004）。在这个功能性 CD8（+）IFN-γ（+）IL-2（-）群体中，CD45RA（+）趋化因子（C-C）受体 7（CCR7）（-）表型的细胞与症状评分呈负相关，具有肺归巢和细胞毒性潜力。在缺乏交叉中和抗体的情况下，针对保守病毒表位的 CD8（+）T 细胞与针对症状性流感的交叉保护相关。这种保护性免疫相关性可以指导通用流感疫苗的开发。
