T cell activation in a murine model of asthma.
Krinzman, Stephen J, George T. De Sanctis, Manuela Cernadas, Lester
Kobzik, James A. Listman, David C. Christiani, David L. Perkins, and
Patricia W. Finn.
Department of Medicine, Pulmonary Divisions, Massachusetts General
Hospital, Brigham and Women's Hospital and Beth Israel Hospital;
Nephrology Division, Brigham and Women's Hospital; Pathology
Department, Brigham and Women's Hospital , Harvard University School
of Medicine, Boston, Massachusetts, USA, 02112
APStracts 3:0066L, 1996.
To determine the mechanisms by which inhaled antigens produce
pulmonary inflammation and bronchial hyperreactivity, we have
developed a murine model of asthma. BALB/c mice are sensitized and
challenged with ovalbumin (OVA). Compared to mice treated with
phosphate buffered saline (PBS), OVA treated mice developed increased
lung resistance, decreased dynamic compliance and greater
methacholine reactivity. Bronchoalveolar lavage fluid revealed
significant increases in the proportion of neutrophils and
eosinophils. Tissue sections of OVA treated mice demonstrated goblet
-cell metaplasia and focal perivascular and peribronchial infiltrates
composed of lymphocytes, neutrophils and eosinophils. Analysis of
thoracic lymphocytes via flow cytometry revealed an expansion of both
CD4+ and B cell populations, with increased expression of
interleukin-2 receptor on CD4+ T cells, indicated increased
activation. There was also increased expression of CD44 on CD4+ and
CD8+ lymphocytes, suggesting an expansion of the local memory-cell
population. These findings support the hypothesis that activation of
T lymphocytes mediates allergic pulmonary inflammation and bronchial
reactivity in asthma.
Received 1 September 1995; accepted in final form 27 March 1996.
APS Manuscript Number L267-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96