Airway Hyperresponsiveness through Synergy of γδ T Cells and NKT Cells

Abstract

Mice sensitized and challenged with OVA were used to investigate the role of innate T cells in the development of allergic airway hyperresponsiveness (AHR). AHR, but not eosinophilic airway inflammation, was induced in T cell-deficient mice by small numbers of cotransferred γδ T cells and invariant NKT cells, whereas either cell type alone was not effective. Only Vγ1+Vδ5+ γδ T cells enhanced AHR. Surprisingly, OVA-specific αβ T cells were not required, revealing a pathway of AHR development mediated entirely by innate T cells. The data suggest that lymphocytic synergism, which is key to the Ag-specific adaptive immune response, is also intrinsic to T cell-dependent innate responses.

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

“…iNKT cells have also been reported to synergize with γδ T cells in a model of allergic airway hyperresponsiveness [58], although the mechanism of cooperation between these two cell types remains unknown.…”

ICOS/ICOSL Interaction Is Required for CD4+ Invariant NKT Cell Function and Homeostatic Survival

“…The requirement for iNKT cells was specific, since adoptive transfer of iNKT cells from wildtype (WT) mice reconstituted the development of AHR in iNKT cell-deficient J␣18 Ϫ/Ϫ mice. These studies of iNKT cells in mice and nonhuman primates (1)(2)(3)(4)(5)(6)(7)(8) strongly suggest that iNKT cells play an important role in human asthma. Indeed, a significant number of CD4…”

“…It is characterized by inflammation in the peribronchial space, with increased production of airway mucus, and by airway hyperreactivity (AHR), 3 a cardinal feature of asthma. Although conventional CD4…”

Toll-Like Receptor 3 Ligand Dampens Liver Inflammation by Stimulating Vα14 Invariant Natural Killer T Cells to Negatively Regulate γδT Cells

“…17,36,40 Numerous studies have used ␥␦T cell-deficient mice and/or ␥␦T celldepleting antibody to confirm a regulatory role for ␥␦T cells in the pathophysiology of numerous infectious and autoimmune diseases. 17,36,40 However, just one study 62 has attempted to investigate whether ␥␦T cells and V␣14iNKT cells are functionally linked in vivo. Specifically, Jin et al 62 reported that either ␥␦T cells or V␣14iNKT cells alone were ineffective in mediating allergic airway hyperresponsiveness and the synergy of both cells was required to mediate lung inflammation and injury associated with airway hyperresponsiveness.…”

“…17,36,40 However, just one study 62 has attempted to investigate whether ␥␦T cells and V␣14iNKT cells are functionally linked in vivo. Specifically, Jin et al 62 reported that either ␥␦T cells or V␣14iNKT cells alone were ineffective in mediating allergic airway hyperresponsiveness and the synergy of both cells was required to mediate lung inflammation and injury associated with airway hyperresponsiveness. As discussed above, we observed that V␣14iNKT cell deficiency was associated with increased accumulation of intrahepatic ␥␦T cells on poly I:C treatment.…”