Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses

J Immunol. 2014 Jul 15;193(2):871-8. doi: 10.4049/jimmunol.1302429. Epub 2014 Jun 9.


The role of the TNF family member CD70 in adaptive T cell responses has been intensively studied, but its function in innate responses is still under investigation. In this study, we show that CD70 inhibits the early innate response to murine CMV (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70(-/-) mice reacted to MCMV infection with a robust type I IFN and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70(-/-) mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70(-/-) mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naive CD70(-/-) mice were not as efficient at suppressing T cell proliferation compared with Treg from naive wild-type mice, and depletion of Treg during MCMV infection in Foxp3-diphtheria toxin receptor mice or in wild-type mice recapitulated the phenotype observed in CD70(-/-) mice. Our study demonstrates that although CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function.

Publication types

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

MeSH terms

  • Adaptive Immunity / genetics
  • Adaptive Immunity / immunology*
  • Animals
  • CD27 Ligand / genetics
  • CD27 Ligand / immunology*
  • CD27 Ligand / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / blood
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / virology
  • Host-Pathogen Interactions / immunology
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muromegalovirus / immunology*
  • Muromegalovirus / physiology
  • Spleen / immunology
  • Spleen / metabolism
  • Survival Analysis
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Time Factors


  • CD27 Ligand
  • Cytokines
  • Interferon-gamma