Differential role of IL-2R signaling for CD8+ T cell responses in acute and chronic viral infections

Eur J Immunol. 2007 Jun;37(6):1502-12. doi: 10.1002/eji.200637023.

Abstract

IL-2 is a cytokine with multiple and even divergent functions; it has been described as a key cytokine for in vitro T cell proliferation but is also essential for down-regulating T cell responses by inducing activation-induced cell death as well as regulatory T cells. The in vivo analysis of IL-2 function in regulating specific T cell responses has been hampered by the fact that mice deficient in IL-2 or its receptors develop lymphoproliferative diseases and/or autoimmunity. Here we generated chimeric mice harboring both IL-2R-competent and IL-2R-deficient T cells and assessed CD8+ T cell induction, function and maintenance after acute or persistent viral infections. Induction and maintenance of CD8+ T cells were relatively independent of IL-2R signaling during acute/resolved viral infection. In marked contrast, IL-2 was crucial for secondary expansion of memory CD8+ T cells and for the maintenance of virus-specific CD8+ T cells during persistent viral infections. Thus, depending on the chronicity of antigen exposure, IL-2R signaling is either essential or largely dispensable for induction and maintenance of virus-specific CD8+ T cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Viral / immunology
  • Bone Marrow Transplantation
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Chronic Disease
  • Epitopes, T-Lymphocyte / immunology
  • Glycoproteins / immunology
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / physiology
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • L-Selectin / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Lysosome-Associated Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / physiology*
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Proteins / immunology
  • Virus Diseases / immunology*

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Lysosome-Associated Membrane Glycoproteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Viral Proteins
  • glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
  • L-Selectin
  • Interferon-gamma