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

Autor(es)

de-Oliveira, Marilia G. ^[1] ; Lira, Aline A. L. ^[1] ; Sgnotto, Fabio R. ^[2] ; Inoue, Amanda H. S. ^[1] ; Santos, Ludimila S. ^{[3, 1]} ; Nakamatsu, Bernardo Y. ^[3] ; Duarte, Alberto J. S. ^{[4, 1]} ; Leite-de-Moraes, Maria ^[5] ; Victor, Jefferson R. ^{[3, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Med Sch, Div Clin Dermatol, Lab Med Invest LIM 56, Av Dr Eneas de Carvalho Aguiar 500, 3rd Floor, BR-05403000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Med Sch, Div Hematol, Sao Paulo - Brazil

^[3] Laureate Int Univ, FMU, Div Environm Hlth, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Med Sch, Div Pathol, Sao Paulo - Brazil

^[5] Univ Paris 05, Lab Immunoregulat & Immunopathol, INEM, CNRS UMR8253, INSERM, UMR1151, Paris - France

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL AND EXPERIMENTAL ALLERGY; v. 49, n. 7, p. 1000-1012, JUL 2019.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 17/18558-9 - Avaliação in vitro da influência do repertório IgG murino sobre a maturação de linfócitos B e Tgamma-delta com potencial regulador e/ou modulador
• Beneficiário: Amanda Harumi Sabô Inoue
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/05181-7 - Avaliação translacional do efeito modulador e/ou regulador dos anticorpos IgG na maturação de linfócitos TCD4, TCD8, nTreg, Tgammadelta e B intra-tímicos de neonatos.
• Beneficiário: Alberto José da Silva Duarte
• Modalidade de apoio: Auxílio à Pesquisa - Regular