Protective CD8 T cell memory is impaired during chronic CD70-driven costimulation

J Immunol. 2009 May 1;182(9):5352-62. doi: 10.4049/jimmunol.0802809.

Abstract

Chronic infection results in continuous formation and exhaustion of effector CD8 T cells and in failure of memory CD8 T cell development. Expression of CD70 and other molecules that provide costimulation to T cells is maintained during chronic infection. To analyze the impact of constitutive CD70-driven costimulation, we generated transgenic mice expressing CD70 specifically on T cells. We show that CD70 promoted accumulation of CD8 T cells with characteristics strikingly similar to exhausted effector CD8 T cells found during chronic infection. CD70 on T cells provided costimulation that enhanced primary CD8 T cell responses against influenza. In contrast, memory CD8 T cell maintenance and protection against secondary challenge with influenza was impaired. Interestingly, we found no effect on the formation of either effector or memory CD4 T cells. We conclude that constitutive expression of CD70 is sufficient to deregulate the CD8 T cell differentiation pathway of acute infection reminiscent of events in chronic infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • CD27 Ligand / biosynthesis
  • CD27 Ligand / deficiency
  • CD27 Ligand / genetics
  • CD27 Ligand / physiology*
  • CD8-Positive T-Lymphocytes / classification
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Chronic Disease
  • Homeostasis / genetics
  • Homeostasis / immunology
  • Immunologic Memory* / genetics
  • Influenza A Virus, H1N1 Subtype / immunology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / pathology
  • Lymphocytic Choriomeningitis / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / pathology
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology*

Substances

  • CD27 Ligand