title: Differential role for T cells in the development of fibrotic lesions associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia versus Acute Respiratory Distress Syndrome.
abstract: Bronchiolitis obliterans organizing pneumonia (BOOP) and Acute Respiratory Distress Syndrome (ARDS) are two pulmonary diseases with fibrotic components. BOOP is characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intra-alveolar fibrosis. ARDS is a biphasic disease that includes an acute phase, consisting of severe leukocyte infiltration, edema, hemorrhage, and the formation of hyaline membranes, and a chronic phase, which is characterized by persistent intra-alveolar and interstitial fibrosis. CBA/J mice infected with 1 x 10(6) plaque-forming units (pfu) reovirus 1/L develop follicular bronchiolitis and intra-alveolar fibrosis similar to BOOP. In contrast, CBA/J mice infected with 1 x 10(7) pfu reovirus 1/L develop histologic characteristics of ARDS including diffuse alveolar damage, hyaline membranes, and intra-alveolar fibrosis. In this report, we demonstrate a differential role for T lymphocytes in the development of fibrosis associated with BOOP versus ARDS. Neonatally thymectomized CBA/J mice infected with 1 x 10(7) pfu (ARDS) reovirus 1/L still develop the hallmark characteristics of ARDS, including a severe viral pneumonia with cellular infiltrates comprised mainly of macrophages and neutrophils, hyaline membrane formation, and hemorrhage during the acute phase of the disease and persistent intra-alveolar fibrosis during the chronic phase of the disease. In contrast, neonatally thymectomized CBA/J mice infected with 1 x 10(6) pfu (BOOP) reovirus 1/L do not develop intra-alveolar fibrosis associated with BOOP. Therefore, while T cells are necessary for the development of intraluminal fibrosis associated with BOOP, they are not necessary for the development of intraluminal fibrosis associated with ARDS. Furthermore, we suggest that interferon-gamma plays a key role in the fibrotic process and that elevated levels of interferon-gamma are associated with a continuum from least to more severe fibrosis.
authors.affiliation: Department of Microbiology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Majeski
authors.forename: Russell A
authors.initials: RA
authors.lastname: Harley
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bellum
authors.forename: Steven D
authors.initials: SD
authors.lastname: London
authors.forename: Lucille
authors.initials: L
authors.lastname: London
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics; D018549:Cryptogenic Organizing Pneumonia / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D030102:Orthoreovirus, Mammalian / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma