Specific maternal microchimeric T cells targeting fetal antigens in β cells predispose to auto-immune diabetes in the child

Roy, Edwige, Leduc, Michele, Guegan, Sarah, Rachdi, Latif, Kluger, Nicolas, Scharfmann, Raphael, Aractingi, Selim and Khosrotehrani, Kiarash (2011) Specific maternal microchimeric T cells targeting fetal antigens in β cells predispose to auto-immune diabetes in the child. Journal of Autoimmunity, 36 3-4: 253-262. doi:10.1016/j.jaut.2011.02.003


Author Roy, Edwige
Leduc, Michele
Guegan, Sarah
Rachdi, Latif
Kluger, Nicolas
Scharfmann, Raphael
Aractingi, Selim
Khosrotehrani, Kiarash
Title Specific maternal microchimeric T cells targeting fetal antigens in β cells predispose to auto-immune diabetes in the child
Journal name Journal of Autoimmunity   Check publisher's open access policy
ISSN 0896-8411
1095-9157
Publication date 2011-05
Sub-type Article (original research)
DOI 10.1016/j.jaut.2011.02.003
Volume 36
Issue 3-4
Start page 253
End page 262
Total pages 10
Place of publication London, United Kingdom
Publisher Academic Press
Collection year 2012
Language eng
Formatted abstract
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 β 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.
Keyword Microchimerism
Pregnancies
Auto-immune diabetes
Maternal cells
T cells
Insulitis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2012 Collection
School of Medicine Publications
 
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Created: Wed, 19 Oct 2011, 12:10:11 EST by Dr Kiarash Khosrotehrani on behalf of Medicine - Princess Alexandra Hospital