Proinflammatory roles of T-cell receptor (TCR)γδ and TCRαβ lymphocytes in a murine model of asthma

The role of lymphocytes bearing αβ or γδ 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 TCRβ(-/-) and TCRδ(-/-) 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 10⁴ cells), peribronchial lympho-plasmocytic infiltration, and elevated serum IgE (4.9 ± 0.6 μg/ml). These responses were markedly attenuated in TCRδ(-/-) animals (5.0 ± 1.0 X 10⁴ eosinophils and 1.6 ± 0.3 μg/ml IgE) and were completely absent in TCRβ(-/-) mice (< 1 x 10³ eosinophils and 0.38 ± 0.21 μg/ml IgE). Similar results were observed in mice treated with anti-TCRγδ or anti-TCRαβ monoclonal antibodies. Airway responsiveness to aerosolized methacholine was also reduced in challenged TCRδ(-/-) animals relative to challenged wild-type mice. These results demonstrate that acute allergic airway responses are dependent upon intact TCRαβ and TCRγδ lymphocyte function and that TCRγδ cells promote acute airway sensitization.