Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1305-1312 |
| Number of pages | 8 |
| Journal | Nature Medicine |
| Volume | 19 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2013 |
Bibliographical note
Funding Information:We thank all the willing participants of the study, with special thanks to M. Blokpoel and T. Williams. We also thank M. Bautista, S. Bowes, B. Fortunaso and S. Lloyd-James for processing all the samples and M. Magtoto, S. Bremang, L. Grass and L. Potiphar for recruiting the participants. We thank S. Ritter (University of California, Berkeley) for his contribution to the figures, K. Roberts and P. Stilwell from Imperial College London for help with growing the virus and E. Rubin (Harvard University), E. Tchillian and P. Beverley (University of Oxford) for their input and insightful discussions S.S. is supported by the Imperial College National Health Service Healthcare Trust. S.B. is supported by a Medical Research Council PhD studentship. A.L. is a Wellcome Trust Senior Research Fellow in Clinical Science and a National Institute of Health Research Senior Investigator. The funders had no input in the design or conduct of the study, the collection, management, analysis or interpretation of the data or the preparation, review or approval of the manuscript. A.L. and S.S. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
