The effects of maternal type 1 diabetes on autoreactive CD4+ T cells in neonates

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Abstract Summary

The risk of developing type 1 diabetes is decreased in children born to mothers with type 1 diabetes as compared to children with a father or sibling with type 1 diabetes. We hypothesized that protection is provided by the increased proinsulin and insulin production by the fetus during a maternal type 1 diabetes pregnancy via an increased efficiency of (pro)insulin-specific T cell removal and regulation. To test this, CD4+ T cell responses to proinsulin and insulin were examined at birth in children who had a father or sibling with type 1 diabetes (n=14), a mother with type 1 diabetes (n=15) or without a first degree family history of type 1 diabetes (n=16). Multi-parametric flow cytometry analysis identified increased hematopoietic stem cell numbers in cord blood from children with diabetic mothers (p=0.002). The frequencies of responding CD4+ T cells to proinsulin (p=0.0046) and to insulin (p=0.0009) were increased in neonates with fathers or siblings with type 1 diabetes as compared to neonates of non-diabetic parents and to neonates with mothers with type 1 diabetes (p=0.0027 and 0.0046). Single cell gene expression profiling of proinsulin-responsive CD4+ T cells at birth showed reduced Th1 and Th17 profiles (CTLA4, p p<0.0001; CCR3p<0.0001; CCR5, p=0.0001; CCR6, p=0.0008; AHR, p=0.0008 and RORA, p=0.0009) in neonates of mothers with type 1 diabetes compared to children with a father or sibling with T1D. In samples taken after birth, the ability of Treg cells to suppress proinsulin-specific CD4+ T cells was increased in children of mothers with type 1 diabetes compared to children with another first degree T1D patient (p=0.0016). These findings suggest that increased (pro)insulin production by the fetus during maternal type 1 diabetes gestation favors central and peripheral tolerance to these key targets of autoimmunity in type 1 diabetes.

Submission ID :
IDS2470
Submission Type
Abstract Topics
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany
Forschergruppe Diabetes, Technische Universität München, at Klinikum rechts der Isar, Munich, Germany; Forschergruppe Diabetes e.V. at Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany
CRTD-DFG Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany
CRTD Center for Regenerative Therapies Dresden
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany
CRTD Center for Regenerative Therapies Dresden

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IDS75126
Poster Session A
Poster and oral
Dr Michelle So
9 visits

KEY DATES

Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

Early registration deadline:
Monday 3 September 2018

Registration deadline:
Monday 15 October 2018

Contact
British Society for Immunology
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