期刊
JOURNAL OF AUTOIMMUNITY
卷 36, 期 3-4, 页码 253-262出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2011.02.003
关键词
Microchimerism; Pregnancy; Auto-immune diabetes; Maternal cells; T cells; Insulitis
类别
资金
- Universite Pierre et Marie Curie [BQR 2005]
- French ministry of Education
- ANR-Physio
Objective: During pregnancy there is an exchange of cells between the fetus and the mother including T lymphocytes that can persist after delivery. Previous studies have described an increased numbers of maternal cells in children with juvenile diabetes as compared to their unaffected siblings. Our objective was to assess the possibility for these chimeric T cells to trigger an anti-beta cell response. Research design and methods: We mated OT2 transgenic female mice having T cells specifically targeting ovalbumin to RIP-OVA males expressing ovalbumin in pancreatic beta cells. This allowed us to examine RIP-OVA progeny from OT2 mothers to assess the consequences of maternal T cells acquired during gestation or lactation. We quantitatively analyzed the pancreas of RIP-OVA mice from OT2 mothers for islet infiltration and compared them to RIP-OVA mice not exposed to OT2 mothers or to wild-type mice from OT2 mothers. Results: RIP-OVA mice from OT2 mothers had significantly more peri-insulitis (p = 0.0083) compared to wild-type littermates. Similarly RIP-OVA mice from OT2 mothers had more peri-insulitis as compared to RIP-OVA mice from RIP-OVA mothers (p = 0.0073). Presence and specific anti-ovalbumin activity of maternal OT2 cells in the offsprings' peripheral lymphoid tissues was found in a separate group of mice. In animals presenting islet inflammation, CD3+ infiltrating cells in the pancreas were however derived from the offspring and not from OT2 mothers. In accordance, OT2 and RIP-OVA double transgenic mice with high levels of auto-reactive T cells had more peri-insulitis and sometimes intense insulitis when they were from OT2 mothers as compared to RIP-OVA mothers (p = 0.046). Conclusions: In highly specific fetal/maternal combinations, maternal T cells with activity against the offspring pancreatic beta cells, presumably chimeric in fetal organs, initiate islet inflammation and may therefore predispose to auto-immune diabetes. (C) 2011 Elsevier Ltd. All rights reserved.
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