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

Abstract

Background The precise mechanism involved in the acquisition of the IL-17+ profile of gamma delta T 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 gamma delta T 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 gamma delta T 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 gamma delta T cells in the thymus and PBMCs from humans. Results Maternal immunization reduced the frequency of spontaneous IL-17-producing gamma delta T 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 gamma delta T cell membranes. The modulatory effect of human IgG on human infant intrathymic and adult peripheral gamma delta T cells showed similarities to murine gamma delta T 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 gamma delta T cell maturation. Furthermore, we suggest that IgG is an unprecedented modulatory factor of murine and human gamma delta T cells. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.