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(American Journal of Pathology. 1999;154:1911-1921.)
© 1999 American Society for Investigative Pathology

Regular Articles

Shifts in Lung Lymphocyte Profiles Correlate with the Sequential Development of Acute Allergic and Chronic Tolerant Stages in a Murine Asthma Model

Carmen A. Yiamouyiannis*{dagger}, Craig M. Schramm{dagger}, Lynn Puddington{ddagger}, Peter Stengel§, Ebrahim Baradaran-Hosseini{ddagger}, Walter W. Wolyniec, Herbert E. Whiteley|| and Roger S. Thrall{ddagger}

From the Department of Biology,*
Capital Community Technical College, Hartford, Connecticut; the Departments of Pediatrics{dagger}
and Medicine,{ddagger}
University of Connecticut School of Medicine, Farmington, Connecticut; Boehringer-Ingelheim Pharmaceuticals, Inc.,
Ridgefield, Connecticut; and Department of Pathobiology,||
University of Connecticut, Storrs, Connecticut, and Eli Lilly and Company,§
Lilly Research Laboratories, Indianapolis, Indiana

T lymphocytes have a central regulatory role in the pathogenesis of asthma. We delineated the participation of lymphocytes in the acute allergic and chronic tolerant stages of a murine model of asthma by characterizing the various subsets of lymphocytes in bronchoalveolar lavage and lung tissue associated with these responses. Acute (10-day) aerosol challenge of immunized C57BL/6J mice with ovalbumin resulted in airway eosinophilia, histological evidence of peribronchial and perivascular airway inflammation, clusters of B cells and TCR{gamma}{delta} cells in lung tissue, increased serum IgE levels, and airway hyperresponsiveness to methacholine. In mice subjected to chronic (6-week) aerosol challenge with ovalbumin, airway inflammation and serum IgE levels were significantly attenuated and airway hyperresponsiveness was absent. The marked increases in lung B and T cell populations seen in the acute stage were also significantly reduced in the chronic stage of this model. Thus, acute ovalbumin challenge resulted in airway sensitization characteristic of asthma, whereas chronic ovalbumin challenge elicited a suppressed or tolerant state. The transition from antigenic sensitization to tolerance was accompanied by shifts in lymphocyte profiles in the lung and bronchoalveolar lavage fluid.




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