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

Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15154-9. doi: 10.1073/pnas.0406649101. Epub 2004 Oct 11.

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-15Ralpha and persist longer by homeostatic proliferation. (ii) At the individual cell level, IL-15 induces higher levels of surface coreceptor CD8alphabeta, increasing functional avidity. IL-15 during priming selects or induces higher-avidity CTLs. Conversely, high-avidity CTLs are diminished in IL-15Ralpha knockout mice. These results provide an explanation of CD8+ T cell avidity maturation and may contribute to the design of novel vaccines.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Female
  • Homeostasis
  • Immunologic Memory
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Models, Immunological
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / deficiency
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Il15ra protein, mouse
  • Interleukin-15
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2
  • Recombinant Proteins