Pulmonary immunity to viral infection: adenovirus infection of lung dendritic cells renders T cells nonresponsive to interleukin-2

J Virol. 2006 Feb;80(4):1826-36. doi: 10.1128/JVI.80.4.1826-1836.2006.

Abstract

Adenovirus (Ad) infection has been identified as predisposing hosts to the development of pulmonary disease through unknown mechanisms. Lung dendritic cells (DCs) are vital for initiating pulmonary immune responses; however, the effects of Ad infection on primary lung DC have not been studied. In contrast to the effects on bone marrow- and monocyte-derived DCs, the current study shows that Ad infection of murine BALB/c lung DCs in vitro and in vivo suppresses DC-induced T-cell proliferation. The effect of Ad on DCs was not due to a downregulation of major histocompatibility complex or costimulatory molecules. Analysis of the production of interleukin-12 (IL-12), alpha interferon (IFN-alpha), and IFN-gamma by the Ad-infected DCs shows no significant differences over noninfected control lung DCs. Ad-induced suppression was not due to a deficiency of IL-2 or other DC-secreted factors and was dependent on viral protein synthesis, as UV irradiation of Ad abrogated the suppressive effect. Results suggest that Ad-infected DCs induce T cells to be nonresponsive to IL-2 during primary coculture, as the addition of IL-2 in secondary cultures recovered T-cell proliferation. In vivo studies supported in vitro results showing that Ad infection resulted in lung T cells with decreased proliferative ability. This study demonstrates that Ad infection induces local immunoincompetence by altering DC-T-cell interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae Infections / immunology*
  • Animals
  • Cell Line
  • Cell Proliferation
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology*
  • Disease Models, Animal
  • Female
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class II / analysis
  • Interferon-alpha / biosynthesis
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Respiratory Tract Infections / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Interferon-alpha
  • Interleukin-2
  • Interferon-gamma