Specific maternal microchimeric T cells targeting fetal antigens in β cells predispose to auto-immune diabetes in the child
Identifieur interne : 006714 ( Main/Exploration ); précédent : 006713; suivant : 006715Specific maternal microchimeric T cells targeting fetal antigens in β cells predispose to auto-immune diabetes in the child
Auteurs : Edwige Roy [France] ; Michele Leduc [France] ; Sarah Guegan [France] ; Latif Rachdi [France] ; Nicolas Kluger [France] ; Raphael Scharfmann [France] ; Selim Aractingi [France] ; Kiarash Khosrotehrani [France, Australie]Source :
- Journal of autoimmunity : (Print) [ 0896-8411 ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Diabète, Enfant, Immunologie.
English descriptors
- KwdEn :
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.
Affiliations:
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aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Fetal Stem Cell Laboratory, 27 rue de Chaligny</s1><s2>75012 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>75012 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Leduc, Michele" sort="Leduc, Michele" uniqKey="Leduc M" first="Michele" last="Leduc">Michele Leduc</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>UPMC Univ Paris 6, UMR_S938</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Fetal Stem Cell Laboratory, 27 rue de Chaligny</s1><s2>75012 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>75012 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Dermatologie</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Guegan, Sarah" sort="Guegan, Sarah" uniqKey="Guegan S" first="Sarah" last="Guegan">Sarah Guegan</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>UPMC Univ Paris 6, UMR_S938</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Fetal Stem Cell Laboratory, 27 rue de Chaligny</s1><s2>75012 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>75012 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Dermatologie</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rachdi, Latif" sort="Rachdi, Latif" uniqKey="Rachdi L" first="Latif" last="Rachdi">Latif Rachdi</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>INSERM U845, Centre de Recherche Croissance et Signalisation</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Université Paris Descartes, Faculté de Médecine Necker</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Kluger, Nicolas" sort="Kluger, Nicolas" uniqKey="Kluger N" first="Nicolas" last="Kluger">Nicolas Kluger</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>UPMC Univ Paris 6, UMR_S938</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Fetal Stem Cell Laboratory, 27 rue de Chaligny</s1><s2>75012 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>75012 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Scharfmann, Raphael" sort="Scharfmann, Raphael" uniqKey="Scharfmann R" first="Raphael" last="Scharfmann">Raphael Scharfmann</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>INSERM U845, Centre de Recherche Croissance et Signalisation</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Université Paris Descartes, Faculté de Médecine Necker</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Aractingi, Selim" sort="Aractingi, Selim" uniqKey="Aractingi S" first="Selim" last="Aractingi">Selim Aractingi</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>UPMC Univ Paris 6, UMR_S938</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Fetal Stem Cell Laboratory, 27 rue de Chaligny</s1><s2>75012 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>75012 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Dermatologie</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Khosrotehrani, Kiarash" sort="Khosrotehrani, Kiarash" uniqKey="Khosrotehrani K" first="Kiarash" last="Khosrotehrani">Kiarash Khosrotehrani</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>UPMC Univ Paris 6, UMR_S938</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Fetal Stem Cell Laboratory, 27 rue de Chaligny</s1><s2>75012 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>75012 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Dermatologie</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>The University of Queensland, Centre for Clinical Research (UQCCR)</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of autoimmunity : (Print)</title><title level="j" type="abbreviated">J. autoimmun. : (Print)</title><idno type="ISSN">0896-8411</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of autoimmunity : (Print)</title><title level="j" type="abbreviated">J. autoimmun. : (Print)</title><idno type="ISSN">0896-8411</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigen</term><term>Autoimmune disease</term><term>Child</term><term>Diabetes mellitus</term><term>Fetus</term><term>Immunology</term><term>Insulitis</term><term>Microchimerism</term><term>Mother</term><term>Predisposition</term><term>Pregnancy</term><term>T-Lymphocyte</term><term>β Cell</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Diabète</term><term>Insulite</term><term>Maladie autoimmune</term><term>Lymphocyte T</term><term>Enfant</term><term>Cellule β</term><term>Mère</term><term>Antigène</term><term>Foetus</term><term>Microchimérisme</term><term>Gestation</term><term>Prédisposition</term><term>Immunologie</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Diabète</term><term>Enfant</term><term>Immunologie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement><orgName><li>Université Paris-Descartes</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Roy, Edwige" sort="Roy, Edwige" uniqKey="Roy E" first="Edwige" last="Roy">Edwige Roy</name></region><name sortKey="Aractingi, Selim" sort="Aractingi, Selim" uniqKey="Aractingi S" first="Selim" last="Aractingi">Selim Aractingi</name><name sortKey="Aractingi, Selim" sort="Aractingi, Selim" uniqKey="Aractingi S" first="Selim" last="Aractingi">Selim Aractingi</name><name sortKey="Aractingi, Selim" sort="Aractingi, Selim" uniqKey="Aractingi S" first="Selim" last="Aractingi">Selim Aractingi</name><name sortKey="Guegan, Sarah" sort="Guegan, Sarah" uniqKey="Guegan S" first="Sarah" last="Guegan">Sarah Guegan</name><name sortKey="Guegan, Sarah" sort="Guegan, Sarah" uniqKey="Guegan S" first="Sarah" last="Guegan">Sarah Guegan</name><name sortKey="Guegan, Sarah" sort="Guegan, Sarah" uniqKey="Guegan S" first="Sarah" last="Guegan">Sarah Guegan</name><name sortKey="Khosrotehrani, Kiarash" sort="Khosrotehrani, Kiarash" uniqKey="Khosrotehrani K" first="Kiarash" last="Khosrotehrani">Kiarash Khosrotehrani</name><name sortKey="Khosrotehrani, Kiarash" sort="Khosrotehrani, Kiarash" uniqKey="Khosrotehrani K" first="Kiarash" last="Khosrotehrani">Kiarash Khosrotehrani</name><name sortKey="Khosrotehrani, Kiarash" sort="Khosrotehrani, Kiarash" uniqKey="Khosrotehrani K" first="Kiarash" last="Khosrotehrani">Kiarash Khosrotehrani</name><name sortKey="Kluger, Nicolas" sort="Kluger, Nicolas" uniqKey="Kluger N" first="Nicolas" last="Kluger">Nicolas Kluger</name><name sortKey="Kluger, Nicolas" sort="Kluger, Nicolas" uniqKey="Kluger N" first="Nicolas" last="Kluger">Nicolas Kluger</name><name sortKey="Leduc, Michele" sort="Leduc, Michele" uniqKey="Leduc M" first="Michele" last="Leduc">Michele Leduc</name><name sortKey="Leduc, Michele" sort="Leduc, Michele" uniqKey="Leduc M" first="Michele" last="Leduc">Michele Leduc</name><name sortKey="Leduc, Michele" sort="Leduc, Michele" uniqKey="Leduc M" first="Michele" last="Leduc">Michele Leduc</name><name sortKey="Rachdi, Latif" sort="Rachdi, Latif" uniqKey="Rachdi L" first="Latif" last="Rachdi">Latif Rachdi</name><name sortKey="Rachdi, Latif" sort="Rachdi, Latif" uniqKey="Rachdi L" first="Latif" last="Rachdi">Latif Rachdi</name><name sortKey="Roy, Edwige" sort="Roy, Edwige" uniqKey="Roy E" first="Edwige" last="Roy">Edwige Roy</name><name sortKey="Scharfmann, Raphael" sort="Scharfmann, Raphael" uniqKey="Scharfmann R" first="Raphael" last="Scharfmann">Raphael Scharfmann</name><name sortKey="Scharfmann, Raphael" sort="Scharfmann, Raphael" uniqKey="Scharfmann R" first="Raphael" last="Scharfmann">Raphael Scharfmann</name></country><country name="Australie"><noRegion><name sortKey="Khosrotehrani, Kiarash" sort="Khosrotehrani, Kiarash" uniqKey="Khosrotehrani K" first="Kiarash" last="Khosrotehrani">Kiarash Khosrotehrani</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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