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(American Journal of Pathology. 2003;163:1467-1479.)
© 2003 American Society for Investigative Pathology

Respiratory Reovirus 1/L Induction of Intraluminal Fibrosis, a Model of Bronchiolitis Obliterans Organizing Pneumonia, Is Dependent on T Lymphocytes

Elizabeth I. Majeski^*, Manjeet K. Paintlia^*, Andrea D. Lopez^*, Russell A. Harley, Steven D. London^* and Lucille London^*

From the Departments of Microbiology and Immunology,^* and Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina

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 10⁶ 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)- and monocyte chemoattractant protein-1 (MCP-1). Further, treatment of mice with a neutralizing monoclonal antibody to IFN- 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_H1-derived cytokines, especially IFN-, may play a key role in fibrotic lesion development.

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