Allergic airway hyperresponsiveness-enhancing gammadelta T cells develop in normal untreated mice and fail to produce IL-4/13, unlike Th2 and NKT cells.
Allergic airway hyperresponsiveness (AHR) in OVA-sensitized and challenged mice, mediated by allergen-specific Th2 cells and Th2-like invariant NKT (iNKT) cells, develops under the influence of enhancing and inhibitory gammadelta T cells. The AHR-enhancing cells belong to the Vgamma1(+) gammadelta T cell subset, cells that are capable of increasing IL-5 and IL-13 levels in the airways in a manner like Th2 cells. They also synergize with iNKT cells in mediating AHR. However, unlike Th2 cells, the AHR enhancers arise in untreated mice, and we show here that they exhibit their functional bias already as thymocytes, at an HSA(high) maturational stage. In further contrast to Th2 cells and also unlike iNKT cells, they could not be stimulated to produce IL-4 and IL-13, consistent with their synergistic dependence on iNKT cells in mediating AHR. Mice deficient in IFN-gamma, TNFRp75, or IL-4 did not produce these AHR-enhancing gammadelta T cells, but in the absence of IFN-gamma, spontaneous development of these cells was restored by adoptive transfer of IFN-gamma-competent dendritic cells from untreated donors. The i.p. injection of OVA/aluminum hydroxide restored development of the AHR enhancers in all of the mutant strains, indicating that the enhancers still can be induced when they fail to develop spontaneously, and that they themselves need not express TNFRp75, IFN-gamma, or IL-4 to exert their function. We conclude that both the development and the cytokine potential of the AHR-enhancing gammadelta T cells differs critically from that of Th2 cells and NKT cells, despite similar influences of these cell populations on AHR.
Jin
Niyun
N
Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA.
Roark
Christina L
CL
Miyahara
Nobuaki
N
Taube
Christian
C
Aydintug
M Kemal
MK
Wands
J M
JM
Huang
Yafei
Y
Hahn
Youn-Soo
YS
Gelfand
Erwin W
EW
O'Brien
Rebecca L
RL
Born
Willi K
WK
D000818:Animals; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D055611:Natural Killer T-Cells / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D018793:Interleukin-13; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4; D010047:Ovalbumin