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Virtual memory cells make a major contribution to the response of aged influenza-naive mice to influenza virus infection.

ABSTRACT: Background:A diverse repertoire of naïve T cells is thought to be essential for a robust response to new infections. However, a key aspect of aging of the T cell compartment is a decline in numbers and diversity of peripheral naïve T cells. We have hypothesized that the age-related decline in naïve T cells forces the immune system to respond to new infections using cross-reactive memory T cells generated to previous infections that dominate the aged peripheral T cell repertoire. Results:Here we confirm that the CD8 T cell response of aged, influenza-naïve mice to primary infection with influenza virus is dominated by T cells that derive from the memory T cell pool. These cells exhibit the phenotypic characteristics of virtual memory cells rather than true memory cells. Furthermore, we find that the repertoire of responding CD8 T cells is constrained compared with that of young mice, and differs significantly between individual aged mice. After infection, these virtual memory CD8 T cells effectively develop into granzyme-producing effector cells, and clear virus with kinetics comparable to naïve CD8 T cells from young mice. Conclusions:The response of aged, influenza-naive mice to a new influenza infection is mediated largely by memory CD8 T cells. However, unexpectedly, they have the phenotype of VM cells. In response to de novo influenza virus infection, the VM cells develop into granzyme-producing effector cells and clear virus with comparable kinetics to young CD8 T cells.

SUBMITTER: Lanzer KG

PROVIDER: S-EPMC6081820 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Virtual memory cells make a major contribution to the response of aged influenza-naïve mice to influenza virus infection.

Lanzer Kathleen G KG Cookenham Tres T Reiley William W WW Blackman Marcia A MA

Immunity & ageing : I & A 20180808

<h4>Background</h4>A diverse repertoire of naïve T cells is thought to be essential for a robust response to new infections. However, a key aspect of aging of the T cell compartment is a decline in numbers and diversity of peripheral naïve T cells. We have hypothesized that the age-related decline in naïve T cells forces the immune system to respond to new infections using cross-reactive memory T cells generated to previous infections that dominate the aged peripheral T cell repertoire.<h4>Resul ...[more]

PMID: 30093911

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Dataset Information

Virtual memory cells make a major contribution to the response of aged influenza-naive mice to influenza virus infection.

Publications

Virtual memory cells make a major contribution to the response of aged influenza-naïve mice to influenza virus infection.

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