Vγ4+ γδ T cells regulate airway hyperreactivity to methacholine in ovalbumin-sensitized and challenged mice

被引:64
作者
Hahn, YS
Taube, C
Jin, N
Takeda, K
Park, JW
Wands, JM
Aydintug, MK
Roark, CL
Lahn, M
O'Brien, RL
Gelfand, EW
Born, WK
机构
[1] Natl Jewish Med & Res Ctr, Dept Immunol, Denver, CO 80206 USA
[2] Natl Jewish Med & Res Ctr, Dept Pediat, Div Cell Biol, Denver, CO 80206 USA
[3] Chungbuk Natl Univ, Dept Pediat, Cheongju, South Korea
[4] Coll Med, Cheongju, South Korea
关键词
D O I
10.4049/jimmunol.171.6.3170
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:3170 / 3178
页数:9
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