Proinflammatory roles of T-cell receptor (TCR)gamma delta and TCR alpha beta lymphocytes in a murine model of asthma

The role of lymphocytes bearing alpha beta or gamma delta 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 characteriz ed in wild-type C57BL/6J mice and congenic TCR beta(-/-) and TCR delta(-/-) mice by evaluation of airway eosinophilia, histopathology, serum immunoglo bulin (Ig)E levels, and in vivo airway responsiveness to methacholine. OVA- challenged wild-type mice demonstrated marked pulmonary inflammation, evide nced by airway eosinophilia (68 +/- 7 x 10(4) cells). peribronchial lympho- plasmocytic infiltration, and elevated serum IgE (4.9 +/- 0.6 mu g/ml). The se responses were markedly attenuated in TCR delta(-/-) animals (5.0 +/- 1. 0 x 10(4) eosinophils and 1.6 +/- 0.3 mu g/ml IgE) and were completely abse nt in TCR beta(-/-) mice ( < 1 X 10(3) eosinophils and 0.38 +/- 0.21 mu g/m l IgE). Similar results were observed in mice treated with anti-TCR gamma d elta or anti-TCR alpha beta monoclonal antibodies. Airway responsiveness to aerosolized methacholine was also reduced in challenged TCR delta(-/-) ani mals relative to challenged wild-type mice. These results demonstrate that acute allergic airway responses are dependent upon intact TCR alpha beta an d TCR gamma delta lymphocyte function and that TCR gamma delta cells promot e acute airway sensitization.