Respiratory reovirus 1/L induction of intraluminal fibrosis, a model of bronchiolitis obliterans organizing pneumonia, is dependent on T lymphocytes.
Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinical syndrome characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intraalveolar fibrosis. We have developed an animal model of BOOP where CBA/J mice infected with 1 x 10(6) plaque-forming units (PFU) reovirus 1/L develop follicular bronchiolitis and intraalveolar fibrosis similar to human BOOP. In this report, we demonstrate a role for T cells in the development of intraluminal fibrosis associated with BOOP. Corticosteroid treatment of reovirus 1/L-infected mice both inhibited the development of fibrotic lesions when administered early in the time-course and promoted the resolution of fibrotic lesions when corticosteroid administration was delayed. Further, the depletion of either CD4(+) or CD8(+) T cells before reovirus 1/L infection also inhibited fibrotic lesion development. Both corticosteroid treatment and depletion of CD4(+) or CD8(+) T cells also resulted in decreased expression of the proinflammatory and profibrotic cytokines, interferon (IFN)-gamma and monocyte chemoattractant protein-1 (MCP-1). Further, treatment of mice with a neutralizing monoclonal antibody to IFN-gamma also significantly inhibited the development of fibrosis. Taken together, these results suggest a significant role for T cells in the development of reovirus 1/L-induced BOOP fibrotic lesions in CBA/J mice and suggests that T(H)1-derived cytokines, especially IFN-gamma, may play a key role in fibrotic lesion development.
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D018549:Cryptogenic Organizing Pneumonia / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007937:Leukapheresis; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008775:Methylprednisolone / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D009296:Nasal Cavity / Q000821:virology; D030102:Orthoreovirus, Mammalian; D011658:Pulmonary Fibrosis / Q000473:pathology / Q000503:physiopathology* / Q000821:virology*; D012088:Reoviridae Infections / Q000150:complications*; D013601:T-Lymphocytes
D018925:Chemokines; D016207:Cytokines; D005938:Glucocorticoids; D008775:Methylprednisolone