Hapten-immune pulmonary interstitial fibrosis (HIPIF) in mice requires both CD4+ and CD8+ T lymphocytes.
We present a description and analysis of a mouse model for pulmonary interstitial fibrosis that is induced by a specific immune response to a small reactive chemical group called trinitrophenyl. We describe the model, and then we examine the cellular mechanism for the induction of the fibrosis. The specific increase in hydroxyproline reached a peak by day 7 and persisted through day 28 in all animals that were sensitized to and challenged with the hapten. Distinct patterns of fibrosis that were seen histologically correlated with antigenic pretreatment and were dependent on T lymphocytes. We also report that the inflammatory and fibrotic responses could be adoptively transferred with immune lymphocytes but not with immune serum. In vivo administration of anti-CD4 and anti-CD8 monoclonal antibodies to sensitized mice prevented the development of immune-mediated lung inflammation and was effective in reducing hydroxyproline deposition. We conclude that (activated) T lymphocytes contribute to the pathogenesis of pulmonary fibrotic diseases. The possibility arises that haptens in the environment may promote sensitization of individuals via their skin or lungs and cell-mediated immune responses to haptenated antigens within the lung may promote pulmonary fibrosis.
Hu
H
H
Department of Medicine, University of Miami School of Medicine, Florida 33101.
Stein-Streilein
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000941:Antigens / Q000032:analysis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis* / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006241:Haptens / Q000276:immunology* / Q000494:pharmacology; D006909:Hydroxyproline / Q000032:analysis / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D014301:Trinitrobenzenes / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000941:Antigens; D016827:CD8 Antigens; D006241:Haptens; D014301:Trinitrobenzenes; D006909:Hydroxyproline