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Age-related changes in memory and effector T cells responding to influenza A/H3N2 and pandemic A/H1N1 strains in humans.

ABSTRACT: Age-dependent changes in the cellular immune response have been mainly described in CD8+ T cells, with relative sparing of CD4+ T cells. We show that in older compared to young adults, effector memory and effector CD8+ T-cell subsets responding to influenza A/H3N2 challenge have diminished cytolytic activity. In contrast, effector CD4+ T-cell subsets in older adults share similar phenotypic and functional characteristics with those from young adults. Further, we observed a diminished cytolytic T-cell response to both seasonal influenza A/H3N2 and pandemic H1N1 (pH1N1) strains in older compared to young adults who had received seasonal influenza vaccine. These results are consistent with the observed rates of serious complications from seasonal and pandemic influenza infections in different age groups, and suggest that CD4+ T cells may provide a compensatory response to influenza infection when CD8+ T cells become compromised during the aging process.

SUBMITTER: Zhou X

PROVIDER: S-EPMC3057414 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Age-related changes in memory and effector T cells responding to influenza A/H3N2 and pandemic A/H1N1 strains in humans.

Zhou Xin X McElhaney Janet E JE

Vaccine 20110301 11

Age-dependent changes in the cellular immune response have been mainly described in CD8+ T cells, with relative sparing of CD4+ T cells. We show that in older compared to young adults, effector memory and effector CD8+ T-cell subsets responding to influenza A/H3N2 challenge have diminished cytolytic activity. In contrast, effector CD4+ T-cell subsets in older adults share similar phenotypic and functional characteristics with those from young adults. Further, we observed a diminished cytolytic T ...[more]

PMID: 21353149

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Project description:Pandemic (H1N1) 2009 influenza is affecting countries in all five continents, with most cases so far having been reported in North and South America and Europe, and children and young adults being the most susceptible age groups. To date, the clinical course of disease is typically mild, with low hospitalization and mortality rates. Pandemic (H1N1) 2009 is susceptible to oseltamivir and, although few clinical data are yet available, current information suggests that treatment with oseltamivir appears to be beneficial. Only isolated cases of resistance to the drug have been reported to date, in keeping with the low frequency observed in clinical studies involving patients infected with seasonal influenza viruses. Current health authority guidelines recommend the use of oseltamivir in infected adults and children who have or are at elevated risk for severe disease, including pregnant women; use during the pandemic in infants < 1 year has also been authorized in Europe and a number of other countries, including the USA and Canada. Before the onset of the current pandemic, F. Hoffmann-La Roche Ltd expanded annual production capacity for oseltamivir to 400 million treatment courses per year to meet anticipated demand. However, during an influenza pandemic, and despite increased production capabilities, resources are nonetheless likely to be initially in short supply. For this reason, Roche, in line with WHO recommendations, has advocated advance stockpiling of antivirals by governments as a pandemic preparedness measure. Between 2004 and December 2009, 350 million treatment courses were supplied to governments worldwide. Support for developing countries has been a priority. Roche has established a cluster of initiatives aimed at increasing access to Tamiflu for the world's developing economies, including, making donations to the WHO, establishing the Tamiflu Reserves Program (TRP) and sub-licensing and manufacturing contracts with local companies in Asia and Africa. Furthermore, Roche has published a document outlining how it would allocate limited supplies of Tamiflu during a pandemic, which are in line with WHO recommendations stating that 'resources should be used to provide the maximum possible health benefit'. Roche is also offering support such as reprocessing of expiring capsule stocks (in development) and shelf-life extension to support governments in the management of their stockpiles. Clinical studies, either sponsored by or supported by Roche, are in progress. These trials are designed to investigate the effectiveness of oseltamivir in patients infected with the pandemic virus in greater depth, and include high-dose studies, assessment of natural and drug-induced resistance, and response to treatment in high-risk populations such as young infants, immunocompromised patients and the severely ill.

Project description:BACKGROUND:The mortality burden of the 2009 A/H1N1 pandemic remains unclear in many countries due to delays in reporting of death statistics. We estimate the age- and cause-specific excess mortality impact of the pandemic in France, relative to that of other countries and past epidemic and pandemic seasons. METHODS:We applied Serfling and Poisson excess mortality approaches to model weekly age- and cause-specific mortality rates from June 1969 through May 2010 in France. Indicators of influenza activity, time trends, and seasonal terms were included in the models. We also reviewed the literature for country-specific estimates of 2009 pandemic excess mortality rates to characterize geographical differences in the burden of this pandemic. RESULTS:The 2009 A/H1N1 pandemic was associated with 1.0 (95% Confidence Intervals (CI) 0.2-1.9) excess respiratory deaths per 100,000 population in France, compared to rates per 100,000 of 44 (95% CI 43-45) for the A/H3N2 pandemic and 2.9 (95% CI 2.3-3.7) for average inter-pandemic seasons. The 2009 A/H1N1 pandemic had a 10.6-fold higher impact than inter-pandemic seasons in people aged 5-24 years and 3.8-fold lower impact among people over 65 years. CONCLUSIONS:The 2009 pandemic in France had low mortality impact in most age groups, relative to past influenza seasons, except in school-age children and young adults. The historical A/H3N2 pandemic was associated with much larger mortality impact than the 2009 pandemic, across all age groups and outcomes. Our 2009 pandemic excess mortality estimates for France fall within the range of previous estimates for high-income regions. Based on the analysis of several mortality outcomes and comparison with laboratory-confirmed 2009/H1N1 deaths, we conclude that cardio-respiratory and all-cause mortality lack precision to accurately measure the impact of this pandemic in high-income settings and that use of more specific mortality outcomes is important to obtain reliable age-specific estimates.

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Age-related changes in memory and effector T cells responding to influenza A/H3N2 and pandemic A/H1N1 strains in humans.

Publications

Age-related changes in memory and effector T cells responding to influenza A/H3N2 and pandemic A/H1N1 strains in humans.

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