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.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- October 2004
- DOI:
- 10.1073/pnas.0406649101
- Bibcode:
- 2004PNAS..10115154O
- Keywords:
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- IMMUNOLOGY