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

The role of lymphocytes bearing alphabeta or gammadelta 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 TCRbeta(-/-) and TCRdelta(-/-) 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 microg/ml). These responses were markedly attenuated in TCRdelta(-/-) animals (5.0 +/- 1.0 x 10(4) eosinophils and 1.6 +/- 0. 3 microg/ml IgE) and were completely absent in TCRbeta(-/-) mice (< 1 x 10(3) eosinophils and 0.38 +/- 0.21 microg/ml IgE). Similar results were observed in mice treated with anti-TCRgammadelta or anti-TCRalphabeta monoclonal antibodies. Airway responsiveness to aerosolized methacholine was also reduced in challenged TCRdelta(-/-) animals relative to challenged wild-type mice. These results demonstrate that acute allergic airway responses are dependent upon intact TCRalphabeta and TCRgammadelta lymphocyte function and that TCRgammadelta cells promote acute airway sensitization.