Latent Infection with Cytomegalovirus Is Associated with Poor Memory CD4 Responses to Influenza A Core Proteins in the Elderly
Latent Infection with Cytomegalovirus Is Associated with Poor Memory CD4 Responses to Influenza A Core Proteins in the Elderly
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DOI：
10.4049/jimmunol.1303361
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发表时间：
2014-10-01
影响因子：
4.4
通讯作者：
Pawelec, Graham
中科院分区：
文献类型：
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作者：
Derhovanessian, Evelyna;Maier, Andrea B.;Pawelec, Graham
流感仍然是老年人的主要病原体。CMV感染和与之相关的晚期分化T细胞的积累与老年人对流感疫苗接种的抗体反应性差有关，其中大多数是CMV阳性的。然而，CMV感染是否也影响记忆T细胞对流感的反应仍然未知。为了研究这一点，我们在166名荷兰人（平均年龄62.2岁，范围42-82）中评估了T细胞对甲型流感基质蛋白和核蛋白的体外应答，并在来自北美的第二个队列（平均年龄73.1岁，范围65-81，n = 28）中验证了结果。我们发现，不到一半的CMV感染的老年受试者对流感病毒抗原产生了CD 4 T细胞反应，而80%的未感染老年人也是如此。同样比例的年轻受试者拥有甲型流感病毒反应性CD 4 T细胞，有趣的是，无论他们是否感染CMV，情况都是如此。因此，CMV的影响仅见于老年供体，他们可能已暴露于病毒数十年。对甲型流感病毒具有CD 8应答的供体百分比低于具有CD 4应答的供体百分比;这不受试者是否为CMV血清阳性或血清阴性的影响。与CMV感染的无应答者相比，CMV血清阳性应答者的迟分化CD 4 T细胞（CD 45 RA（+/-）CCR 7（-）CD 27（-）CD 28（-））频率显著更高。这些数据增加了越来越多的证据表明，CMV感染对其他病毒产物的反应具有深刻但异质性的影响，并对流感疫苗的设计产生影响，特别是在老年人中。
Influenza remains a major pathogen in older people. Infection with CMV and the accumulation of late-differentiated T cells associated with it have been implicated in poor Ab responsiveness to influenza vaccination in the elderly, most of whom are CMV positive. However, whether CMV infection also affects memory T cell responses to influenza remains unknown. To investigate this, we assessed T cell responses to influenza A matrix protein and nucleoprotein ex vivo in 166 Dutch individuals (mean age 62.2 y, range 42-82) and validated the results in a second cohort from North America (mean age 73.1 y, range 65-81, n = 28). We found that less than half of the CMV-infected older subjects mounted a CD4 T cell response to influenza Ags, whereas similar to 80% of uninfected elderly did so. A similar proportion of younger subjects possessed influenza A virus-responsive CD4 T cells, and, interestingly, this was the case whether they were CMV-infected. Thus, the effect of CMV was only seen in the older donors, who may have been exposed to the virus for decades. The percentage of donors with CD8 responses to influenza A virus was lower than those with CD4; this was not influenced by whether the subjects were CMV seropositive or seronegative. CMV-seropositive responders had significantly higher frequencies of late-differentiated CD4 T-cells (CD45RA(+/-)CCR7(-)CD27(-)CD28(-)) compared with CMV-infected nonresponders. These data add to the accumulating evidence that infection with CMV has profound but heterogeneous effects on responses to the products of other viruses and have implications for the design of influenza vaccines, especially in the elderly.