T cells specific for a bee toxin make mostly IFN-γ and IL-4 before beekeeping season (blue) but mostly IL-10 after the season begins (red).

Beekeepers are the new, improved mouse model for immune responses to allergens, according to a study from Meiler et al. (page 2887). The fleeting tolerance of these intrepid honey lovers to bee antigens is now revealed to require a Jekyll-and-Hyde set of T cells that go from attack to suppressive mode and back again.

It's an immunologist's dream. By the very nature of their jobs, unprotected beekeepers are voluntarily and repeatedly injected with high doses of bee antigen—an average of 13 antigen-loaded stings in the first week of honey-harvesting season alone, according to the study. And in just these seven days, the beekeepers developed an immune tolerance that was noticeable in both skin reactions and T cell responses.

T cells that started out proliferation-happy in response to bee antigen became much more subdued soon after the season began. The authors traced this change to cytokine alterations: within a week, T cells that had made mostly IFN-γ started making more IL-10, which tempers immune reactions. IL-10–producing cells curbed the in vitro proliferation of other T cells in response to bee antigen.

The cytokine switch, the authors found, was initiated through the histamine pathway. As with many allergens, bee venom induces mast cells to unload histamine. In vitro experiments with the beekeepers' T cells revealed that histamine induced IL-10 production and T cell lethargy, both of which required the H2 histamine receptor.

The beekeepers' tolerance was lost within two months of season's end, unveiling a relatively short lifespan of T cell suppression. The cycle repeated at the onset of the next season, so beekeepers have little to worry about. But allergy sufferers, who may be defective in this IL-10 response, might be less enthused, because the findings suggest that successful therapies involving allergen-specific immunotherapy probably require considerable perseverance. NL