Maternal IgG impairs the maturation of offspring intrathymic IL-17-producing γδT cells: Implications for murine and human allergies.

Background: The precise mechanism involved in the acquisition of the IL-17+ profile of γδT cells, the ligands responsible for this change, and whether this default is acquired during intrathymic maturation need to be elucidated.

Objective: This study aimed to evaluate whether IL-17-producing γδT cells are present in the airways of tolerant offspring from allergen-sensitized mothers and the possible implication of maternal IgG in the generation of these cells.

Methods: Female mice were immunized or not, and the allergic response, frequency of γδT cell subsets and cytokine production of the offspring were analysed by flow cytometry. The effects of passive in vivo transfer of purified IgG were investigated in offspring. A translational approach was employed to analyse γδT cells in the thymus and PBMCs from humans.

Results: Maternal immunization reduced the frequency of spontaneous IL-17-producing γδT cells in the thymus, spleen and lung of offspring. This effect was mimicked by the in vivo treatment of females with purified IgG. IgG directly interacted with γδT cell membranes. The modulatory effect of human IgG on human infant intrathymic and adult peripheral γδT cells showed similarities to murine γδT cells, which is rarely reported in the literature.

Conclusions & Clinical Relevance: Together, our results reveal that IgG from potentially tolerant atopic mothers can influence offspring thymic IL-17-producing γδT cell maturation. Furthermore, we suggest that IgG is an unprecedented modulatory factor of murine and human γδT cells. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.