Proinflammatory roles of T-cell receptor (TCR)γδ and TCRαβ 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 characterized in wild-type C57BL/6J mice and congenic TCR beta(-/-) and TCR delta(-/-) 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 x 10(4) cells). peribronchial lympho-plasmocytic infiltration, and elevated serum IgE (4.9 +/- 0.6 mu g/ml). These 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 absent in TCR beta(-/-) mice ( < 1 X 10(3) eosinophils and 0.38 +/- 0.21 mu g/ml IgE). Similar results were observed in mice treated with anti-TCR gamma delta or anti-TCR alpha beta monoclonal antibodies. Airway responsiveness to aerosolized methacholine was also reduced in challenged TCR delta(-/-) animals relative to challenged wild-type mice. These results demonstrate that acute allergic airway responses are dependent upon intact TCR alpha beta and TCR gamma delta lymphocyte function and that TCR gamma delta cells promote acute airway sensitization.