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
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
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DOI：
10.4049/jimmunol.172.6.3437
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发表时间：
2004-03-15
影响因子：
4.4
通讯作者：
Gravenstein, S
中科院分区：
文献类型：
--
作者：
Deng, YP;Jing, Y;Gravenstein, S
本研究的目的是分析与年轻人相比，老年人对流感的1型T细胞反应（包括CD 4（+）Th 1和CD 8（+）T细胞反应）的变化。用流感病毒离体活化的PBMC表现出1型T细胞应答的年龄相关性下降，这通过使用ELISPOT或细胞内细胞因子染色的流感特异性IFN-γ分泌记忆T细胞（IFN-γ（+）ISMT）的频率下降来显示。在老年受试者中，IFN-γ（+）ISMT频率降低伴随着每个细胞IFN-γ分泌水平降低。四聚体染色结合IFN-γ ELISPOT表明，IFN-γ（+）流感M1肽特异性T细胞的下降不是由于T细胞库的消耗，而是由于ISMT随年龄的功能丧失。此外，1型T细胞反应下降。不是由于Th 2应答的增加或老年人APC的缺陷。在老年人中，CTL培养物中流感特异性CD 8（+）T细胞的扩增减少。与年轻受试者相比，体弱的老年受试者也表现出钝化和有点延迟的1型T细胞对流感疫苗接种的反应，这与IgG 1亚型和总抗体反应的减少呈正相关。综上所述，这些数据表明，随着年龄的增长，1型T细胞对流感的反应下降，这可能有助于解释与年龄相关的疫苗有效性下降以及流感发病率和死亡率增加。
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-gamma-secreting memory T cells specific for influenza, (IFN-gamma(+) ISMT) using ELISPOT or intracellular cytokine staining. The reduced frequency of IFN-gamma(+) ISMT was accompanied by a reduced level of IFN-gamma secretion per cell in elderly subjects. Tetramer staining, combined with IFN-gamma ELISPOT, indicated that the decline in IFN-gamma(+), 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.