Reversal of allergic airway hyperreactivity after long-term allergen challenge depends on gammadelta T cells.
Long-term allergen exposure can attenuate inflammation and revert airway hyperreactivity to normal responsiveness. A model of such reversal was established in which airway hyperreactivity and inflammation in ovalbumin-sensitized and challenged mice were decreased after multiple daily airway challenges. This change in responsiveness and inflammation was associated with a transition from a helper T cell Type 2 to a helper T cell Type 1 cytokine-biased profile in bronchoalveolar lavage fluid. Cell transfer from long-term exposed mice into hyperreactive mice also restored normal airway responsiveness, establishing the mechanism underlying the reversal of the hyperreactivity as active suppression, but did not affect eosinophilic airway inflammation. Conversely, airway hyperreactivity, suppressed as a result of long-term allergen exposure, could be reestablished by depleting gammadelta T cells, in particular Vgamma4+ cells. Antigen-specific tolerance of alphabeta T cells or suppression by non-gammadelta T cells did not play a role in the reversal to normal airway responsiveness and gammadelta T cells did not play a role in the regulation of the allergic inflammatory response. These findings show that normal responsiveness in previously hyperreactive mice, achieved after long-term allergen challenge, is based on several, apparently independent regulatory mechanisms. One of these, focused on airway responsiveness, involves active suppression and requires gammadelta T cells.
Cui
Zhi-Hua
ZH
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Joetham
Anthony
A
Aydintug
M Kemal
MK
Hahn
Yoon-Soo
YS
Born
Willi K
WK
Gelfand
Erwin W
EW
D000485:Allergens; D000818:Animals; D001985:Bronchial Provocation Tests; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D012074:Remission Induction; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000503:physiopathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D013997:Time Factors
D000485:Allergens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D010047:Ovalbumin