Abstract
Matured in the thymus, γδT cells can modulate the development of allergy in humans. The main γδT cell subsets have been described as interleukin (IL)-17A or interferon (IFN)-γ producers, but these cells can also produce other modulatory cytokines, such as IL-4 and IL-10. Here, we aimed to evaluate whether IgG can modulate the profile of cytokine production by γδT cells during their maturation in the thymus and after its migration to peripheral tissues. Thymic tissues were obtained from 12 infants, and peripheral blood mononuclear cells (PBMCs) were obtained from adults (both groups without an atopic background). IgG was purified from atopic and non-atopic volunteers. Thymocytes and PBMCs were cultured with purified atopic or non-atopic IgG, and intracellular cytokine production and phenotype were assessed. Mock and IVIg conditions were used as controls. IgG from non-atopic individuals induced IFN-γ and IL-10 production by thymic γδT cells, and no effect was observed on peripheral γδT cells. IL-17 production was inhibited by non-atopic IgG on thymic γδT cells and augmented by atopic IgG on peripheral γδT cells. Modulated thymic γδT cells did not produce IFN-γ and IL-10 simultaneously. We additionally evaluated the phenotype of intrathymic γδT cells and observed that IgG from all groups could induce CD25 expression and could not influence the CD28 expression of these cells. This report describes evidence revealing that IgG may influence the production of IFN-γ and IL-10 by intrathymic γδT cells depending on the donor atopic state. This observation is unprecedented and needs to be considered in further studies in the IgG immunotherapy field.
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Acknowledgements
This study was supported by grants from the Laboratory of Medical Investigation-56, Medical School, University of São Paulo, São Paulo, Brazil (LIM-56 HC-FMUSP); São Paulo Research Foundation (FAPESP—Grant #2018/05181-7) and the São Paulo Administrative Development Foundation (FUNDAP). We also thank Dr. Luciana Bento de Souza Dr. Luciana Bento de Souza for providing technical support in preparing human thymocyte suspensions.
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Santos, L.S., Sgnotto, F.d., Inoue, A.H.S. et al. IgG from Non-atopic Individuals Induces In Vitro IFN-γ and IL-10 Production by Human Intra-thymic γδT Cells: A Comparison with Atopic IgG and IVIg. Arch. Immunol. Ther. Exp. 67, 263–270 (2019). https://doi.org/10.1007/s00005-019-00545-6
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DOI: https://doi.org/10.1007/s00005-019-00545-6