Am. J. Respir. Cell Mol. Biol., Volume 22, Number 2, February, 2000 218-225

Proinflammatory Roles of T-Cell Receptor (TCR) and TCR Lymphocytes in a Murine Model of Asthma

Craig M. Schramm, Lynn Puddington, Carmen A. Yiamouyiannis, Elizabeth G. Lingenheld, Herbert E. Whiteley, Walter W. Wolyniec, Thomas C. Noonan, and Roger S. Thrall

Departments of Pediatrics and Medicine, University of Connecticut School of Medicine, Farmington; Department of Biology, Capital Community Technical College, Hartford; Department of Pathobiology, University of Connecticut, Storrs; and Boehringer-Ingelheim Pharmaceuticals, Incorporated, Ridgefield, Connecticut

The role of lymphocytes bearing or T-cell receptors (TCRs) was assessed during the acute allergic response in a mouse model of asthma. The inflammatory immune response to ovalbumin (OVA) was characterized in wild-type C57BL/6J mice and congenic TCR^/ and TCR^/ mice by evaluation of airway eosinophilia, histopathology, serum immunoglobulin (Ig)E levels, and in vivo airway responsiveness to methacholine. OVA-challenged wild-type mice demonstrated marked pulmonary inflammation, evidenced by airway eosinophilia (68 ± 7 × 10⁴ cells), peribronchial lympho-plasmocytic infiltration, and elevated serum IgE (4.9 ± 0.6 µg/ml). These responses were markedly attenuated in TCR^/ animals (5.0 ± 1.0 × 10⁴ eosinophils and 1.6 ± 0.3 µg/ml IgE) and were completely absent in TCR^/ mice (< 1 × 10³ eosinophils and 0.38 ± 0.21 µg/ml IgE). Similar results were observed in mice treated with anti-TCR or anti-TCR monoclonal antibodies. Airway responsiveness to aerosolized methacholine was also reduced in challenged TCR^/ animals relative to challenged wild-type mice. These results demonstrate that acute allergic airway responses are dependent upon intact TCR and TCR lymphocyte function and that TCR cells promote acute airway sensitization.

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