Fas ligand expression on T cells is sufficient to prevent prolonged airway inflammation in a murine model of asthma

Am J Respir Cell Mol Biol. 2010 Sep;43(3):342-8. doi: 10.1165/rcmb.2008-0454OC. Epub 2009 Oct 23.

Abstract

Our previous studies revealed that, in a murine model of asthma, mice that received Fas-deficient T cells developed a prolonged phase of airway inflammation, mucus production, and airway hyperreactivity that failed to resolve even 6 weeks after the last challenge. To investigate how Fas-Fas ligand (FasL) interaction occurs between T cells and other cells in vivo, Gld mice with abnormalities of the FasL signaling pathway were used. The reconstituted mice were made by transferring T cells from B6 or Gld mice to Rag(-/-) or FasL-deficient Rag(-/-) mice. We found that Rag(-/-) mice that received B6 T cells resolved the airway inflammation, whereas FasL-deficient Rag(-/-) mice that received Gld T cells developed a prolonged airway inflammation at Day 28, with decreased IFN-gamma production. Both FasL-deficient Rag(-/-) mice that received B6 T cells and Rag(-/-) mice that received Gld T cells also had completely resolved their airway inflammation by Day 28 after challenge. Interestingly, FasL-deficient Rag(-/-) mice that received Gld T cells eventually resolved airway inflammation at Day 42, with a similar level of IFN-gamma production to that of control group. These results demonstrate that FasL expression on either T cells only or non-T cells only was sufficient for the eventual resolution of airway inflammation, and the prolonged airway inflammation in FasL-deficient Rag(-/-) mice that received Gld T cells was correlated with decreased IFN-gamma production by Gld T cells.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / prevention & control*
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Fas Ligand Protein / physiology*
  • Flow Cytometry
  • Homeodomain Proteins / physiology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Respiratory System / metabolism*
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / transplantation

Substances

  • Cytokines
  • Fas Ligand Protein
  • Homeodomain Proteins
  • RAG-1 protein