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

SK Oh, LP Perera, DS Burke… - Proceedings of the …, 2004 - National Acad Sciences
SK Oh, LP Perera, DS Burke, TA Waldmann, JA Berzofsky
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
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 …
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.
National Acad Sciences