Cellular immune correlates of protection against symptomatic pandemic influenza
| Autor: | Wendy S. Barclay, Alison Bermingham, William F. Carman, Saranya Sridhar, Shaima Begom, Jonathan J Deeks, Ajit Lalvani, Walt E. Adamson, Thomas Bean, Katja Hoschler |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Cellular immunity Influenza vaccine CD8-Positive T-Lymphocytes Cross Reactions Biology medicine.disease_cause Severity of Illness Index General Biochemistry Genetics and Molecular Biology Epitope Immunophenotyping Cohort Studies Influenza A Virus H1N1 Subtype Immune system Influenza Human Influenza A virus medicine Humans Cytotoxic T cell Heterosubtypic immunity Immunity Cellular General Medicine Virology United Kingdom Virus Shedding Immunology Immunologic Memory CD8 |
| Zdroj: | Nature Medicine. 19:1305-1312 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.3350 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|