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 Vaccination In Vivo in the Elderly

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.

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

“…Recently, it was shown that the numbers of spot-forming cells correlate with clinical protection from culture-confirmed influenza in young children (21). These numbers may vary depending on the antigen type and influenza strain, because median numbers in our assays were higher than those in assays in which hemagglutinin or vaccine components were used (9,(21)(22)(23), and as in the present study, A/H3N2-specific cell-mediated responses were lower than A/H1N1-specific responses. WIV contains core antigens in addition to surface antigens.…”

Discordance between antibody and T cell responses in recipients of trivalent inactivated influenza vaccine

“…The time range of the blood samples taken may account for these results with the second sample ( 13-39 days) which falls within the likely peak of the CD8 T cell response having a more significant effect on the results than the last timepoint sampled. Studies have shown that age impacts T cell responses to influenza vaccination, with elderly individuals (>65 yrs old) showing a decline in type 1 T cell responses which may be a factor in these results; however, the average age of our subjects was 44 years old with no individuals over the age of 60 [39,40]. The role of innate immunity components such as cytokines, dendritic cells, and toll like receptors in initiating influenza specific responses may also contribute to the discordance between these two arms of the immune system.…”

Immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with diabetes mellitus

“…We found that the following [10][11][12] and seasonal influenza vaccine. [13][14][15] Compromised nutritional status [16][17][18] and decreased T-cell activity [18][19][20] could be contributing factors for that finding. One study in patients with hepatitis C reported a decreasing effect of lower BMI on immune response to A(H1N1)pdm09 vaccine.…”