共 31 条
Latent Infection with Cytomegalovirus Is Associated with Poor Memory CD4 Responses to Influenza A Core Proteins in the Elderly
被引:71
作者:
Derhovanessian, Evelyna
[1
]
Maier, Andrea B.
[2
,3
,4
]
Haehnel, Karin
[1
]
McElhaney, Janet E.
[5
]
Slagboom, Eline P.
[3
,6
]
Pawelec, Graham
[1
]
机构:
[1] Univ Tubingen, Med Res Ctr, Dept Internal Med 2, D-72072 Tubingen, Germany
[2] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2333 ZC Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Netherlands Consortium Hlth Aging, NL-2333 ZC Leiden, Netherlands
[4] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-1081 HV Amsterdam, Netherlands
[5] Adv Med Res Inst Canada, Sudbury, ON P3E 5J1, Canada
[6] Leiden Univ, Med Ctr, Sect Mol Epidemiol, Leiden, Netherlands
基金:
加拿大健康研究院;
关键词:
CD8(+) T-CELLS;
OLD-AGE;
IMMUNOSENESCENCE;
VACCINATION;
ACCUMULATION;
PROTECTION;
HUMANS;
PEOPLE;
VIRUS;
CMV;
D O I:
10.4049/jimmunol.1303361
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
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.
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页码:3624 / 3631
页数:8
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