Journal
JOURNAL OF IMMUNOLOGY
Volume 189, Issue 11, Pages 5356-5366Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1201867
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Funding
- U.S. Public Health Service [U51 AI081680]
- National Institute of Allergy and Infectious Diseases [HHSN27220110017C, N01-AI-00017]
- National Institute on Aging/National Institutes of Health [AG20719]
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Persistent CMV infection has been associated with immune senescence. To address the causal impact of lifelong persistent viral infection on immune homeostasis and defense, we infected young mice systemically with HSV-1, murine CMV, or both viruses and studied their T cell homeostasis and function. Herpesvirus(+) mice exhibited increased all-cause mortality compared with controls. Upon Listeria-OVA infection, 23-mo-old animals that had experienced lifelong herpesvirus infections showed impaired bacterial control and CD8 T cell function, along with distinct alterations in the T cell repertoire both before and after Listeria challenge, compared with age-matched, herpesvirus-free controls. Herpesvirus infection was associated with reduced naive CD8 T cell precursors above the loss attributable to aging. Moreover, the OVA-specific CD8 T cell repertoire recruited after Listeria challenge was entirely nonoverlapping between control and herpesvirus(+) mice. To our knowledge, this study for the first time causally links lifelong herpesvirus infection to all-cause mortality in mice and to disturbances in the T cell repertoire, which themselves correspond to impaired immunity to a new infection in aging. The Journal of Immunology, 2012, 189: 5356-5366.
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