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

Oh, SK and Perera, LP and Burke, DS and Waldmann, TA and Berzofsky, JA (2004) IL-15/IL-15Rα-mediated avidity maturation of memory CD8<sup>+</sup> T cells. Proceedings of the National Academy of Sciences of the United States of America, 101 (42). 15154 - 15159. ISSN 0027-8424

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Oh, SK
Perera, LP
Burke, DSdonburke@pitt.eduDONBURKE
Waldmann, TA
Berzofsky, JA
Centers: Other Centers, Institutes, or Units > Center for Vaccine Research
Date: 19 October 2004
Date Type: Publication
Journal or Publication Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 101
Number: 42
Page Range: 15154 - 15159
DOI or Unique Handle: 10.1073/pnas.0406649101
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0027-8424
Date Deposited: 05 May 2015 16:47
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/24327

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