Impairment of bleomycin-induced lung fibrosis in CD28-deficient mice

J Immunol. 2001 Aug 15;167(4):1977-81. doi: 10.4049/jimmunol.167.4.1977.


Lung fibrosis is an important pulmonary disease with a high mortality rate, but its pathophysiological mechanism has not been fully clarified. Various types of cells have been implicated in the development of lung fibrosis, including T cells. However, the contribution of functional molecules expressed on T cells to the development of lung fibrosis remains largely unknown. In this study, we determined whether costimulation via CD28 on T cells was crucial for the development of lung fibrosis by intratracheally administering bleomycin into CD28-deficient mice. Compared with wild-type mice, the CD28-deficient mice showed markedly impaired lung fibrosis after injection with low doses of bleomycin, as judged by histological changes and hydroxyproline content in the lungs. In addition, bleomycin-induced T cell infiltration into the airways and production of several cytokines and chemokines including IL-5 were also impaired in the CD28-deficient mice. Furthermore, adoptive transfer of CD28-positive T cells from wild-type mice recovered the impaired bleomycin-induced lung fibrosis in CD28-deficient mice. These findings suggest that the CD28-mediated T cell costimulation plays a critical role in the development of lung fibrosis, possibly by regulating the production of cytokines and chemokines in the lung. Thus, manipulation of the CD28-mediated costimulation could be a potential therapeutic strategy for the prevention of lung fibrosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, CD / biosynthesis
  • B7-2 Antigen
  • Bleomycin / administration & dosage*
  • CD28 Antigens / genetics*
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Chemokines / antagonists & inhibitors
  • Chemokines / biosynthesis
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Drug
  • Female
  • Intubation, Intratracheal
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / pathology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / genetics*
  • Pulmonary Fibrosis / immunology*
  • Pulmonary Fibrosis / pathology
  • T-Lymphocyte Subsets / transplantation


  • Antigens, CD
  • B7-2 Antigen
  • CD28 Antigens
  • Cd86 protein, mouse
  • Chemokines
  • Cytokines
  • Membrane Glycoproteins
  • Bleomycin