gammadelta T cells contribute to the systemic immunoglobulin E response and local B-cell reactivity in allergic eosinophilic airway inflammation.
Allergic airway inflammation induced in mice is T-cell dependent and recruitment of eosinophils to airspaces requires both alphabeta and gammadelta T cells. From previous studies it is evident that alphabeta T cells are essential for the allergic T helper type 2 (Th2)-like response, while the mechanistic contribution of gammadelta T cells is still unclear. In this study, we have investigated the role of gammadelta T cells in allergic airway eosinophilia induced by ovalbumin hypersensitivity. By comparing the responsiveness to sensitizing allergen of wild-type mice with that of T-cell receptor gammadelta knockout mice (TCRgammadelta KO) we demonstrated that mice lacking gammadelta T cells are defective in the systemic ovalbumin-specific immunoglobulin E (IgE) response. Furthermore, after aerosol challenge with allergen, gammadelta T-cell deficient mice exhibited a significantly decreased migration of B cells and natural killer cells to airways and reduced levels of allergen-specific IgG and IgA in bronchoalveolar lavage fluid. The role for B cells in the airway inflammation was indicated by the impaired ability of mice lacking functional B cells to evoke an eosinophilic response. The diminished eosinophilia in TCRgammadelta KO mice could not be explained by a defective Th2 activation since these mice displayed a normal IgG response in serum and an unaffected IG2b/IgG1 ratio in airways. Analysis of immunoregulatory cytokines in isolated lung tissue, thoracic lymph nodes and spleen further supported the notion that these mice are able to evoke a sufficient activation of T helper cells and that gammadelta T cells are not required for maintaining the Th2 profile. These results indicate that gammadelta T cells contribute to allergic airway inflammation by pathways separate from classical Th2 immune activation.
Svensson
Linda
L
Division of NBC Defence, Swedish Defence Research Agency, Umeå, Sweden.
Lilliehöök
Bo
B
Larsson
Roland
R
Bucht
Anders
A
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007073:Immunoglobulin E