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Proceedings of the National Academy of Sciences
Article . 2004 . Peer-reviewed
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IL-15/IL-15Rα-mediated avidity maturation of memory CD8+T cells

Authors: SangKon, Oh; Liyanage P, Perera; Donald S, Burke; Thomas A, Waldmann; Jay A, Berzofsky;

IL-15/IL-15Rα-mediated avidity maturation of memory CD8+T cells

Abstract

T cell avidity is critical to viral clearance, but mechanisms of CD8+T cell avidity maturation are poorly understood. Here, we find that IL-15 mediates two mechanisms of avidity maturation. (i) By selection at the population level, IL-15 promotes greater survival of high- compared with low-avidity cytotoxic T lymphocytes (CTLs). High-avidity CTLs express higher levels of IL-15Rα and persist longer by homeostatic proliferation. (ii) At the individual cell level, IL-15 induces higher levels of surface coreceptor CD8αβ, increasing functional avidity. IL-15 during priming selects or induces higher-avidity CTLs. Conversely, high-avidity CTLs are diminished in IL-15Rα knockout mice. These results provide an explanation of CD8+T cell avidity maturation and may contribute to the design of novel vaccines.

Keywords

Interleukin-15, Mice, Knockout, Mice, Inbred BALB C, Receptors, Interleukin-15, Models, Immunological, Cell Differentiation, Receptors, Interleukin-2, CD8-Positive T-Lymphocytes, Recombinant Proteins, Mice, Animals, Homeostasis, Female, Immunologic Memory, T-Lymphocytes, Cytotoxic

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    117
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
117
Top 10%
Top 10%
Top 10%
bronze