Cellular immune correlates of protection against symptomatic pandemic influenza

被引：691

作者：

Sridhar, Saranya ^{[1
]}

Begom, Shaima ^{[1
]}

Bermingham, Alison ^{[2
]}

Hoschler, Katja ^{[2
]}

Adamson, Walt ^{[3
]}

Carman, William ^{[4
]}

Bean, Thomas ^{[5
]}

Barclay, Wendy ^{[6
]}

Deeks, Jonathan J. ^{[7
]}

Lalvani, Ajit ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Infect Sect, London, England

[2] Publ Hlth England, Ctr Infect, Resp Virus Unit, London, England

[3] West Scotland Specialist Virol Ctr, Glasgow, Lanark, Scotland

[4] Univ Glasgow, Ctr Virus Res, Glasgow, Lanark, Scotland

[5] Publ Hlth England Microbiol Serv, Porton Down, England

[6] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Virol, London, England

[7] Univ Birmingham, Sch Hlth & Populat Sci, Birmingham, W Midlands, England

来源：

NATURE MEDICINE | 2013年 / 19卷 / 10期

基金：

英国医学研究理事会;

关键词：

TOXIC LYMPHOCYTES-T; A VIRUS-INFECTION; H5N1; INFLUENZA; CROSS-REACT; SELECTIVE ACCUMULATION; LETHAL INFECTION; CELLS; H1N1; MEMORY; MICE;

D O I：

10.1038/nm.3350

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-g (IFN-g)+ interleukin-2 (IL-2)-CD8+ T cells (r = -0.6, P = 0.004). Within this functional CD8+ IFN-g+ IL-2population, 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.

引用

页码：1305 / +

页数：9

共 57 条

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