Lifelong persistent viral infection alters the naive T cell pool, impairing CD8 T cell immunity in late life

Megan J Smithey, Gang Li, Vanessa Venturi, Miles P. Davenport, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5356-5366
Number of pages11
JournalJournal of Immunology
Volume189
Issue number11
DOIs
StatePublished - Dec 1 2012

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Virus Diseases
Immunity
Herpesviridae Infections
Herpesviridae
T-Lymphocytes
Listeria
Homeostasis
T-Lymphoid Precursor Cells
Listeriosis
Mortality
Human Herpesvirus 1
Infection
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Lifelong persistent viral infection alters the naive T cell pool, impairing CD8 T cell immunity in late life. / Smithey, Megan J; Li, Gang; Venturi, Vanessa; Davenport, Miles P.; Nikolich-Zugich, Janko.

In: Journal of Immunology, Vol. 189, No. 11, 01.12.2012, p. 5356-5366.

Research output: Contribution to journalArticle

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