V gamma 4+ gamma delta T cells regulate airway hyperreactivity to methacholine in ovalbumin-sensitized and challenged mice.
The Vgamma4(+) pulmonary subset of gammadelta T cells regulates innate airway responsiveness in the absence of alphabeta T cells. We now have examined the same subset in a model of allergic airway disease, OVA-sensitized and challenged mice that exhibit Th2 responses, pulmonary inflammation, and airway hyperreactivity (AHR). In sensitized mice, Vgamma4(+) cells preferentially increased in number following airway challenge. Depletion of Vgamma4(+) cells before the challenge substantially increased AHR in these mice, but had no effect on airway responsiveness in normal, nonchallenged mice. Depletion of Vgamma1(+) cells had no effect on AHR, and depletion of all TCR-delta(+) cells was no more effective than depletion of Vgamma4(+) cells alone. Adoptively transferred pulmonary lymphocytes containing Vgamma4(+) cells inhibited AHR, but lost this ability when Vgamma4(+) cells were depleted, indicating that these cells actively suppress AHR. Eosinophilic infiltration of the lung and airways, or goblet cell hyperplasia, was not affected by depletion of Vgamma4(+) cells, although cytokine-producing alphabeta T cells in the lung increased. These findings establish Vgamma4(+) gammadelta T cells as negative regulators of AHR and show that their regulatory effect bypasses much of the allergic inflammatory response coincident with AHR.
Hahn
Youn-Soo
YS
Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Taube
Christian
C
Jin
Niyun
N
Takeda
Katsuyuki
K
Park
Jung-Won
JW
Wands
J M
JM
Aydintug
M Kemal
MK
Roark
Christina L
CL
Lahn
Michael
M
O'Brien
Rebecca L
RL
Gelfand
Erwin W
EW
Born
Willi K
WK
D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020397:Goblet Cells / Q000473:pathology; D006965:Hyperplasia; D007114:Immunization; D007274:Injections, Intraperitoneal; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D016210:Methacholine Chloride / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016210:Methacholine Chloride; D010047:Ovalbumin