Cellular immune correlates of protection against symptomatic pandemic influenza

作者：Sridhar, Saranya; Begom, Shaima; Bermingham, Alison; Hoschler, Katja; Adamson, Walt; Carman, William; Bean, Thomas; Barclay, Wendy; Deeks, Jonathan J.; Lalvani, Ajit^*

来源：Nature Medicine, 2013, 19(10): 1305-+.

DOI：10.1038/nm.3350

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

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.

• 出版日期2013-10