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Virtual memory cells make a major contribution to the response of aged influenza-na?ve mice to influenza virus infection

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  • Virtual memory cells make a major contribution to the response of aged influenza-na?ve mice to influenza virus infection

    Immun Ageing. 2018 Aug 8;15:17. doi: 10.1186/s12979-018-0122-y. eCollection 2018.
    Virtual memory cells make a major contribution to the response of aged influenza-na?ve mice to influenza virus infection.

    Lanzer KG1, Cookenham T1, Reiley WW1, Blackman MA1.
    Author information

    Abstract

    Background:

    A diverse repertoire of na?ve 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 na?ve T cells. We have hypothesized that the age-related decline in na?ve 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-na?ve 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 na?ve 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.


    KEYWORDS:

    Ageing; Influenza; Mouse model; T cell receptor repertoire; True memory (TM) T cells; Virtual memory (VM) T cells

    PMID: 30093911 PMCID: PMC6081820 DOI: 10.1186/s12979-018-0122-y
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