IL-21 deficiency influences CD8 T cell quality and recall responses following an acute viral infection

J Immunol. 2010 Oct 15;185(8):4835-45. doi: 10.4049/jimmunol.1001032. Epub 2010 Sep 15.

Abstract

CD4 T cells are principal producers of IL-21 and are often required for optimal CD8 T cell responses. Therefore, we investigated the importance of IL-21 in determining the phenotypic attributes, functional quality, and maintenance of antiviral CD8 T cells following acute infection with the prototypic mouse pathogen lymphocytic choriomeningitis virus. Previous reports have documented an obligatory role for IL-21 in sustaining CD8 T cell responses during chronic infections. Here we show that the requirements for IL-21 are less stringent following acute infections; however, in the absence of IL-21, the capacity of CD8 T cells to attain the polyfunctional trait of IL-2 production is consistently reduced during both the effector and memory phases. This is further supported by in vitro studies showing that the addition of IL-21 promotes the differentiation of IL-2-producing CD8 T cells. Although the generation of memory CD8 T cells, which are capable of mounting protective recall responses, proceeds independently of IL-21, we demonstrate that IL-21 does function to support secondary responses, especially under competitive conditions. Collectively, these studies highlight the potential roles of IL-21 in determining the quality of CD8 T cell responses postinfection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • Flow Cytometry
  • Immunologic Memory / immunology
  • Interleukin-2 / immunology
  • Interleukins / deficiency*
  • Interleukins / immunology
  • Lymphocyte Activation / immunology
  • Lymphocytic Choriomeningitis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic

Substances

  • Interleukin-2
  • Interleukins
  • interleukin-21