Antigen-specific regulation of IgE antibodies by non-antigen-specific γδ T cells.

We re-examined the observation that gamma delta T cells, when transferred from mice tolerized to an inhaled conventional Ag, suppress the allergic IgE response to this Ag specifically. Using OVA and hen egg lysozyme in crisscross fashion, we confirmed the Ag-specific IgE-regulatory effect of the gamma delta T cells. Although only V gamma 4(+) gamma delta T cells are regulators, the Ag specificity does not stem from specificity of their gamma delta TCRs. Instead, the V gamma 4(+) gamma delta T cells failed to respond to either Ag, but rapidly acquired Ag-specific regulatory function in vivo following i.v. injection of non-T cells derived from the spleen of Ag-tolerized mice. This correlated with their in vivo Ag acquisition from i.v. injected Ag-loaded splenic non-T cells, and in vivo transfer of membrane label provided evidence for direct contact between the injected splenic non-T cells and the V gamma 4(+) gamma delta T cells. Together, our data suggest that Ag itself, when acquired by gamma delta T cells, directs the specificity of their IgE suppression. The Journal of Immunology, 2013, 190: 913-921.