Regulatory role of gammadelta T cells in the recruitment of CD4+ and CD8+ T cells to lung and subsequent pulmonary fibrosis

J Immunol. 2006 Oct 1;177(7):4436-43. doi: 10.4049/jimmunol.177.7.4436.

Abstract

The mechanisms by which T cells accumulate in the lungs of patients with pulmonary fibrosis are poorly understood. Because the lung is continually exposed to microbial agents from the environment, we repeatedly exposed C57BL/6 mice to the ubiquitous microorganism, Bacillus subtilis, to determine whether chronic exposure to an inhaled microorganism could lead to T cell accumulation in the lungs and subsequent pulmonary fibrosis. C57BL/6 mice repeatedly treated with B. subtilis for 4 consecutive weeks developed a 33-fold increase in the number of CD4+ T cells and a 354-fold increase in gammadelta T cells in the lung. The gammadelta T cells consisted almost entirely of Vgamma6/Vdelta1+ cells, a murine subset bearing an invariant TCR the function of which is still unknown. Treatment of C57BL/6 mice with heat-killed vs live B. subtilis resulted in a 2-fold increase in the number of CD4+ T cells in the lung but no expansion of gammadelta T cells indicating that gammadelta cells accumulate in response to live microorganisms. In addition, mice treated with heat-killed B. subtilis developed significantly increased pulmonary fibrosis compared with mice treated with the live microorganism. Mice deficient in Vgamma6/Vdelta1+ T cells when treated with B. subtilis had a 231-fold increase in lung CD4+ T cells and significantly increased collagen deposition compared with wild-type C57BL/6 mice, consistent with an immunoregulatory role for the Vgamma6/Vdelta1 T cell subset. These findings indicate that chronic inhalation of B. subtilis can result in T cell accumulation in the lung and fibrosis, constituting a new model of immune-mediated pulmonary fibrosis.

Publication types

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

MeSH terms

  • Animals
  • Bacillus subtilis / immunology
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Count
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Lung / immunology*
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pulmonary Fibrosis / immunology*
  • Pulmonary Fibrosis / microbiology
  • Pulmonary Fibrosis / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Receptors, Antigen, T-Cell, gamma-delta