Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza …

Y Deng, Y Jing, AE Campbell… - The Journal of …, 2004 - journals.aai.org
Y Deng, Y Jing, AE Campbell, S Gravenstein
The Journal of Immunology, 2004journals.aai.org
The objective of this study was to analyze the changes in the type 1 T cell response,
including the CD4+ Th1 and CD8+ T cell responses, to influenza in the elderly compared
with those in young adults. PBMC activated ex vivo with influenza virus exhibited an age-
related decline in type 1 T cell response, shown by the decline in the frequency of IFN-γ-
secreting memory T cells specific for influenza (IFN-γ+ ISMT) using ELISPOT or intracellular
cytokine staining. The reduced frequency of IFN-γ+ ISMT was accompanied by a reduced …
Abstract
The objective of this study was to analyze the changes in the type 1 T cell response, including the CD4+ Th1 and CD8+ T cell responses, to influenza in the elderly compared with those in young adults. PBMC activated ex vivo with influenza virus exhibited an age-related decline in type 1 T cell response, shown by the decline in the frequency of IFN-γ-secreting memory T cells specific for influenza (IFN-γ+ ISMT) using ELISPOT or intracellular cytokine staining. The reduced frequency of IFN-γ+ ISMT was accompanied by a reduced level of IFN-γ secretion per cell in elderly subjects. Tetramer staining, combined with IFN-γ ELISPOT, indicated that the decline in IFN-γ+, influenza M1-peptide-specific T cells was not due to attrition of the T cell repertoire, but, rather, to the functional loss of ISMT with age. In addition, the decline in type 1 T cell response was not due to an increase in Th2 response or defects in APCs from the elderly. The expansion of influenza-specific CD8+ T cells in CTL cultures was reduced in the elderly. Compared with young subjects, frail elderly subjects also exhibited a blunted and somewhat delayed type 1 T cell response to influenza vaccination, which correlated positively with the reduced IgG1 subtype and the total Ab response. Taken together, these data demonstrate that there is a decline in the type 1 T cell response to influenza with age that may help explain the age-related decline in vaccine efficacy and the increases in influenza morbidity and mortality.
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