Proinflammatory roles of T-cell receptor (TCR)gammadelta and TCRalphabeta 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.
Schramm
C M
CM
Departments of Pediatrics and Medicine, University of Connecticut School of Medicine, Farmington, CT, USA. schramm@sun.uchc.edu
Puddington
L
L
Yiamouyiannis
C A
CA
Lingenheld
E G
EG
Whiteley
H E
HE
Wolyniec
W W
WW
Noonan
T C
TC
Thrall
R S
RS
D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000502:physiology*
D018836:Inflammation Mediators; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta