Expansion of CD4+CD25+FOXP3+ regulatory T cells in infants of mothers with type 1 diabetes
Background Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers. Objective To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compare...
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| Published in | Pediatric diabetes Vol. 13; no. 5; pp. 400 - 407 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Denmark
Blackwell Publishing Ltd
01.08.2012
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1399-543X 1399-5448 1399-5448 |
| DOI | 10.1111/j.1399-5448.2012.00852.x |
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| Abstract | Background
Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers.
Objective
To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D.
Subjects and Methods
Cord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)‐10, and transforming growth factor (TGF)‐β was measured by real‐time reverse transcription polymerase chain reaction.
Results
The percentage of FOXP3+ cells in CD4+CD25high cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25high cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL‐10, and TGF‐β transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease‐related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin‐stimulated CBMCs (p = 0.007 and p = 0.014).
Conclusions
We suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes. |
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| AbstractList | Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers.BACKGROUNDReduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers.To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D.OBJECTIVETo evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D.Cord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)-10, and transforming growth factor (TGF)-β was measured by real-time reverse transcription polymerase chain reaction.SUBJECTS AND METHODSCord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)-10, and transforming growth factor (TGF)-β was measured by real-time reverse transcription polymerase chain reaction.The percentage of FOXP3+ cells in CD4+CD25(high) cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25(high) cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL-10, and TGF-β transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease-related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin-stimulated CBMCs (p = 0.007 and p = 0.014).RESULTSThe percentage of FOXP3+ cells in CD4+CD25(high) cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25(high) cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL-10, and TGF-β transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease-related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin-stimulated CBMCs (p = 0.007 and p = 0.014).We suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes.CONCLUSIONSWe suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes. Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers. To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D. Cord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)-10, and transforming growth factor (TGF)- beta was measured by real-time reverse transcription polymerase chain reaction. The percentage of FOXP3+ cells in CD4+CD25high cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25high cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL-10, and TGF- beta transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease-related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin-stimulated CBMCs (p = 0.007 and p = 0.014). We suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes. Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers. To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D. Cord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)-10, and transforming growth factor (TGF)-β was measured by real-time reverse transcription polymerase chain reaction. The percentage of FOXP3+ cells in CD4+CD25(high) cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25(high) cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL-10, and TGF-β transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease-related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin-stimulated CBMCs (p = 0.007 and p = 0.014). We suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes. Background Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers. Objective To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D. Subjects and Methods Cord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)‐10, and transforming growth factor (TGF)‐β was measured by real‐time reverse transcription polymerase chain reaction. Results The percentage of FOXP3+ cells in CD4+CD25high cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25high cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL‐10, and TGF‐β transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease‐related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin‐stimulated CBMCs (p = 0.007 and p = 0.014). Conclusions We suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes. |
| Author | Åkerblom, Hans K Nieminen, Janne K Luopajärvi, Kristiina Knip, Mikael Ilonen, Jorma Vaarala, Outi |
| AuthorAffiliation | b Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland e Folkhälsan Research Center, Helsinki, Finland d Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland c Immunogenetics Laboratory, University of Turku, Turku, Finland f Department of Pediatrics, Tampere University Hospital, Tampere, Finland a Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland |
| AuthorAffiliation_xml | – name: a Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland – name: d Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland – name: f Department of Pediatrics, Tampere University Hospital, Tampere, Finland – name: e Folkhälsan Research Center, Helsinki, Finland – name: b Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland – name: c Immunogenetics Laboratory, University of Turku, Turku, Finland |
| Author_xml | – sequence: 1 givenname: Kristiina surname: Luopajärvi fullname: Luopajärvi, Kristiina email: kristiina.luopajarvi@thl.fi organization: Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Immune Response Unit, Helsinki, Finland – sequence: 2 givenname: Janne K surname: Nieminen fullname: Nieminen, Janne K organization: Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Immune Response Unit, Helsinki, Finland – sequence: 3 givenname: Jorma surname: Ilonen fullname: Ilonen, Jorma organization: Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland – sequence: 4 givenname: Hans K surname: Åkerblom fullname: Åkerblom, Hans K organization: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland – sequence: 5 givenname: Mikael surname: Knip fullname: Knip, Mikael organization: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland – sequence: 6 givenname: Outi surname: Vaarala fullname: Vaarala, Outi organization: Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Immune Response Unit, Helsinki, Finland |
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| References | Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003: 4: 330-336. Palmer JP, Asplin CM, Clemons P et al. Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 1983: 222: 1337-1339. Greenbaum CJ, Palmer JP. Insulin antibodies and insulin autoantibodies. Diabet Med 1991: 8: 97-105. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995: 155: 1151-1164. Pugliese A, Brown D, Garza D et al. Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. J Clin Invest 2001: 107: 555-564. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003: 299: 1057-1061. Harjutsalo V, Reunanen A, Tuomilehto J. Differential transmission of type 1 diabetes from diabetic fathers and mothers to their offspring. Diabetes 2006: 55: 1517-1524. Rudensky AY, Gavin M, Zheng Y. FOXP3 and NFAT: partners in tolerance. Cell 2006: 126: 253-256. Sjöroos M, Iitiä A, Ilonen J, Reijonen H, Lövgren T. Triple-label hybridization assay for type-1 diabetes-related HLA alleles. BioTechniques 1995: 18: 870-877. DiMario U, Fallucca F, Gargiulo P et al. Insulin-anti-insulin complexes in diabetic women and their neonates. Diabetologia 1984: 27 (Suppl.): 83-86. The EURODIAB ACE Study Group and the EURODIAB ACE Substudy 2 Study Group. Familial risk of type I diabetes in European children. Diabetologia 1998: 41: 1151-1156. Knip M, Lautala P, Leppäluoto J, Åkerblom HK, Kouvalainen K. Relation of enteroinsular hormones at birth to macrosomia and neonatal hypoglycemia in infants of diabetic mothers. J Pediatr 1983: 103: 603-611. Tanaka S, Maeda S, Hashimoto M et al. Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function. J Immunol 2010: 185: 2295-2305. Hölttä V, Klemetti P, Sipponen T et al. IL-23/IL-17 immunity as a hallmark of crohn's disease. Inflamm Bowel Dis 2008: 14: 1175-1184. Laine AP, Holmberg H, Nilsson A et al. Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations. Dis Markers 2007: 23: 139-145. Fineberg SE, Kawabata TT, Finco-Kent D, Fountaine RJ, Finch GL, Krasner AS. Immunological responses to exogenous insulin. Endocr Rev 2007: 28: 625-652. Pugliese A, Zeller M, Fernandez A et al. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet 1997: 15: 293-297. Oh-hora M, Yamashita M, Hogan PG et al. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat Immunol 2008: 9: 432-443. Warram JH, Krolewski AS, Gottlieb MS, Kahn CR. Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N Engl J Med 1984: 311: 149-152. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008: 133: 775-787. Tuomilehto J, Podar T, Tuomilehto-Wolf E, Virtala E. Evidence for importance of gender and birth cohort for risk of IDDM in offspring of IDDM parents. Diabetologia 1995: 38: 975-982. TRIGR Study Group. Study design of the trial to reduce IDDM in the genetically at risk (TRIGR). Pediatr Diabetes 2007: 8: 117-137. Hermann R, Lipponen K, Kiviniemi M et al. Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes. Diabetologia 2006: 49: 1198-1208. Menon RK, Cohen RM, Sperling MA, Cutfield WS, Mimouni F, Khoury JC. Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. Its role in fetal macrosomia. N Engl J Med 1990: 323: 309-315. Vang T, Congia M, Macis MD et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 2005: 37: 1317-1319. Walker MR, Kasprowicz DJ, Gersuk V et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 2003: 112: 1437-1443. Laaksonen M, Pastinen T, Sjöroos M et al. HLA class II associated risk and protection against multiple sclerosis-a Finnish family study. J Neuroimmunol 2002: 122: 140-145. Aarnisalo J, Treszl A, Svec P et al. Reduced CD4+ T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant. J Autoimmun 2008: 31: 13-21. Potter KN, Wilkin TJ. The molecular specificity of insulin autoantibodies. Diabetes Metab Res Rev 2000: 16: 338-353. Stanford S, Mustelin T, Bottini N. Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases. Semin Immunopathol 2010: 32: 127-136. Kiviniemi M, Nurmi J, Turpeinen H, Lövgren T, Ilonen J. A homogeneous high-throughput genotyping method based on competitive hybridization. Clin Biochem 2003: 36: 633-640. Warram JH, Martin BC, Krolewski AS. Risk of IDDM in children of diabetic mothers decreases with increasing maternal age at pregnancy. Diabetes 1991: 40: 1679-1684. Paronen J, Knip M, Savilahti E et al. Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish trial to reduce IDDM in the genetically at risk study group. Diabetes 2000: 49: 1657-1665. Kukko M, Virtanen SM, Toivonen A et al. Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country. Diabetes Care 2004: 27: 676-681. 2010; 32 2000; 49 1990; 323 1995; 38 1984; 27 2004; 27 2006; 55 2008; 9 2008; 14 2003; 36 2010; 185 1995; 155 1995; 18 2008; 31 1998; 41 2001; 107 2003; 112 2003; 299 1991; 8 2007; 28 1983; 103 1983; 222 2000; 16 1984; 311 1997; 15 2006; 49 2002; 122 1991; 40 2007; 8 2003; 4 2005; 37 2008; 133 2006; 126 2007; 23 |
| References_xml | – reference: Laaksonen M, Pastinen T, Sjöroos M et al. HLA class II associated risk and protection against multiple sclerosis-a Finnish family study. J Neuroimmunol 2002: 122: 140-145. – reference: Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003: 299: 1057-1061. – reference: Palmer JP, Asplin CM, Clemons P et al. Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 1983: 222: 1337-1339. – reference: Aarnisalo J, Treszl A, Svec P et al. Reduced CD4+ T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant. J Autoimmun 2008: 31: 13-21. – reference: Pugliese A, Brown D, Garza D et al. Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. J Clin Invest 2001: 107: 555-564. – reference: TRIGR Study Group. Study design of the trial to reduce IDDM in the genetically at risk (TRIGR). Pediatr Diabetes 2007: 8: 117-137. – reference: Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008: 133: 775-787. – reference: Knip M, Lautala P, Leppäluoto J, Åkerblom HK, Kouvalainen K. Relation of enteroinsular hormones at birth to macrosomia and neonatal hypoglycemia in infants of diabetic mothers. J Pediatr 1983: 103: 603-611. – reference: Laine AP, Holmberg H, Nilsson A et al. Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations. Dis Markers 2007: 23: 139-145. – reference: Warram JH, Martin BC, Krolewski AS. Risk of IDDM in children of diabetic mothers decreases with increasing maternal age at pregnancy. Diabetes 1991: 40: 1679-1684. – reference: Tuomilehto J, Podar T, Tuomilehto-Wolf E, Virtala E. Evidence for importance of gender and birth cohort for risk of IDDM in offspring of IDDM parents. Diabetologia 1995: 38: 975-982. – reference: Hölttä V, Klemetti P, Sipponen T et al. IL-23/IL-17 immunity as a hallmark of crohn's disease. Inflamm Bowel Dis 2008: 14: 1175-1184. – reference: Menon RK, Cohen RM, Sperling MA, Cutfield WS, Mimouni F, Khoury JC. Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. Its role in fetal macrosomia. N Engl J Med 1990: 323: 309-315. – reference: Warram JH, Krolewski AS, Gottlieb MS, Kahn CR. Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N Engl J Med 1984: 311: 149-152. – reference: Vang T, Congia M, Macis MD et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 2005: 37: 1317-1319. – reference: Potter KN, Wilkin TJ. The molecular specificity of insulin autoantibodies. Diabetes Metab Res Rev 2000: 16: 338-353. – reference: Greenbaum CJ, Palmer JP. Insulin antibodies and insulin autoantibodies. Diabet Med 1991: 8: 97-105. – reference: Rudensky AY, Gavin M, Zheng Y. FOXP3 and NFAT: partners in tolerance. Cell 2006: 126: 253-256. – reference: Hermann R, Lipponen K, Kiviniemi M et al. Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes. Diabetologia 2006: 49: 1198-1208. – reference: Harjutsalo V, Reunanen A, Tuomilehto J. Differential transmission of type 1 diabetes from diabetic fathers and mothers to their offspring. Diabetes 2006: 55: 1517-1524. – reference: Stanford S, Mustelin T, Bottini N. Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases. Semin Immunopathol 2010: 32: 127-136. – reference: Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003: 4: 330-336. – reference: Kiviniemi M, Nurmi J, Turpeinen H, Lövgren T, Ilonen J. A homogeneous high-throughput genotyping method based on competitive hybridization. Clin Biochem 2003: 36: 633-640. – reference: Fineberg SE, Kawabata TT, Finco-Kent D, Fountaine RJ, Finch GL, Krasner AS. Immunological responses to exogenous insulin. Endocr Rev 2007: 28: 625-652. – reference: Tanaka S, Maeda S, Hashimoto M et al. Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function. J Immunol 2010: 185: 2295-2305. – reference: Oh-hora M, Yamashita M, Hogan PG et al. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat Immunol 2008: 9: 432-443. – reference: Kukko M, Virtanen SM, Toivonen A et al. Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country. Diabetes Care 2004: 27: 676-681. – reference: The EURODIAB ACE Study Group and the EURODIAB ACE Substudy 2 Study Group. Familial risk of type I diabetes in European children. Diabetologia 1998: 41: 1151-1156. – reference: Sjöroos M, Iitiä A, Ilonen J, Reijonen H, Lövgren T. Triple-label hybridization assay for type-1 diabetes-related HLA alleles. BioTechniques 1995: 18: 870-877. – reference: Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995: 155: 1151-1164. – reference: Pugliese A, Zeller M, Fernandez A et al. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet 1997: 15: 293-297. – reference: Walker MR, Kasprowicz DJ, Gersuk V et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 2003: 112: 1437-1443. – reference: Paronen J, Knip M, Savilahti E et al. Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish trial to reduce IDDM in the genetically at risk study group. Diabetes 2000: 49: 1657-1665. – reference: DiMario U, Fallucca F, Gargiulo P et al. Insulin-anti-insulin complexes in diabetic women and their neonates. Diabetologia 1984: 27 (Suppl.): 83-86. – volume: 41 start-page: 1151 year: 1998 end-page: 1156 article-title: Familial risk of type I diabetes in European children publication-title: Diabetologia – volume: 299 start-page: 1057 year: 2003 end-page: 1061 article-title: Control of regulatory T cell development by the transcription factor Foxp3 publication-title: Science – volume: 8 start-page: 117 year: 2007 end-page: 137 article-title: Study design of the trial to reduce IDDM in the genetically at risk (TRIGR) publication-title: Pediatr Diabetes – volume: 323 start-page: 309 year: 1990 end-page: 315 article-title: Transplacental passage of insulin in pregnant women with insulin‐dependent diabetes mellitus. Its role in fetal macrosomia publication-title: N Engl J Med – volume: 55 start-page: 1517 year: 2006 end-page: 1524 article-title: Differential transmission of type 1 diabetes from diabetic fathers and mothers to their offspring publication-title: Diabetes – volume: 16 start-page: 338 year: 2000 end-page: 353 article-title: The molecular specificity of insulin autoantibodies publication-title: Diabetes Metab Res Rev – volume: 37 start-page: 1317 year: 2005 end-page: 1319 article-title: Autoimmune‐associated lymphoid tyrosine phosphatase is a gain‐of‐function variant publication-title: Nat Genet – volume: 23 start-page: 139 year: 2007 end-page: 145 article-title: Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations publication-title: Dis Markers – volume: 185 start-page: 2295 year: 2010 end-page: 2305 article-title: Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function publication-title: J Immunol – volume: 4 start-page: 330 year: 2003 end-page: 336 article-title: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells publication-title: Nat Immunol – volume: 103 start-page: 603 year: 1983 end-page: 611 article-title: Relation of enteroinsular hormones at birth to macrosomia and neonatal hypoglycemia in infants of diabetic mothers publication-title: J Pediatr – volume: 107 start-page: 555 year: 2001 end-page: 564 article-title: Self‐antigen‐presenting cells expressing diabetes‐associated autoantigens exist in both thymus and peripheral lymphoid organs publication-title: J Clin Invest – volume: 49 start-page: 1657 year: 2000 end-page: 1665 article-title: Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish trial to reduce IDDM in the genetically at risk study group publication-title: Diabetes – volume: 15 start-page: 293 year: 1997 end-page: 297 article-title: The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR‐IDDM2 susceptibility locus for type 1 diabetes publication-title: Nat Genet – volume: 126 start-page: 253 year: 2006 end-page: 256 article-title: FOXP3 and NFAT: partners in tolerance publication-title: Cell – volume: 31 start-page: 13 year: 2008 end-page: 21 article-title: Reduced CD4+ T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant publication-title: J Autoimmun – volume: 9 start-page: 432 year: 2008 end-page: 443 article-title: Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance publication-title: Nat Immunol – volume: 8 start-page: 97 year: 1991 end-page: 105 article-title: Insulin antibodies and insulin autoantibodies publication-title: Diabet Med – volume: 311 start-page: 149 year: 1984 end-page: 152 article-title: Differences in risk of insulin‐dependent diabetes in offspring of diabetic mothers and diabetic fathers publication-title: N Engl J Med – volume: 32 start-page: 127 year: 2010 end-page: 136 article-title: Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases publication-title: Semin Immunopathol – volume: 28 start-page: 625 year: 2007 end-page: 652 article-title: Immunological responses to exogenous insulin publication-title: Endocr Rev – volume: 18 start-page: 870 year: 1995 end-page: 877 article-title: Triple‐label hybridization assay for type‐1 diabetes‐related HLA alleles publication-title: BioTechniques – volume: 38 start-page: 975 year: 1995 end-page: 982 article-title: Evidence for importance of gender and birth cohort for risk of IDDM in offspring of IDDM parents publication-title: Diabetologia – volume: 222 start-page: 1337 year: 1983 end-page: 1339 article-title: Insulin antibodies in insulin‐dependent diabetics before insulin treatment publication-title: Science – volume: 122 start-page: 140 year: 2002 end-page: 145 article-title: HLA class II associated risk and protection against multiple sclerosis‐a Finnish family study publication-title: J Neuroimmunol – volume: 49 start-page: 1198 year: 2006 end-page: 1208 article-title: Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes publication-title: Diabetologia – volume: 36 start-page: 633 year: 2003 end-page: 640 article-title: A homogeneous high‐throughput genotyping method based on competitive hybridization publication-title: Clin Biochem – volume: 40 start-page: 1679 year: 1991 end-page: 1684 article-title: Risk of IDDM in children of diabetic mothers decreases with increasing maternal age at pregnancy publication-title: Diabetes – volume: 27 start-page: 676 year: 2004 end-page: 681 article-title: Geographical variation in risk HLA‐DQB1 genotypes for type 1 diabetes and signs of beta‐cell autoimmunity in a high‐incidence country publication-title: Diabetes Care – volume: 155 start-page: 1151 year: 1995 end-page: 1164 article-title: Immunologic self‐tolerance maintained by activated T cells expressing IL‐2 receptor alpha‐chains (CD25). Breakdown of a single mechanism of self‐tolerance causes various autoimmune diseases publication-title: J Immunol – volume: 133 start-page: 775 year: 2008 end-page: 787 article-title: Regulatory T cells and immune tolerance publication-title: Cell – volume: 112 start-page: 1437 year: 2003 end-page: 1443 article-title: Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25‐ T cells publication-title: J Clin Invest – volume: 14 start-page: 1175 year: 2008 end-page: 1184 article-title: IL‐23/IL‐17 immunity as a hallmark of crohn's disease publication-title: Inflamm Bowel Dis – volume: 27 start-page: 83 issue: Suppl. year: 1984 end-page: 86 article-title: Insulin‐anti‐insulin complexes in diabetic women and their neonates publication-title: Diabetologia |
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Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers.... Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers. To evaluate the... Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers.BACKGROUNDReduced... Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers. To evaluate the... |
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| SubjectTerms | CD25 antigen CD4 antigen CD4 Antigens - blood Children Cord blood Diabetes mellitus Diabetes Mellitus, Type 1 - drug therapy Diabetes Mellitus, Type 1 - immunology Female Fetal Blood - immunology Fetuses Flow cytometry Forkhead Transcription Factors - blood Foxp3 protein Gene expression Humans Immunoregulation Infant Infant, Newborn Infants Insulin Insulin - therapeutic use insulin treatment Interleukin 10 Interleukin-2 Receptor alpha Subunit - blood Leukocytes (mononuclear) Lymphocytes T Male Mothers Polymerase chain reaction Progeny Protein-tyrosine-phosphatase regulatory T cells Reverse transcription Risk factors STIM1 protein T-Lymphocytes, Regulatory - immunology T1D Transforming growth factor Transforming growth factor- beta |
| Title | Expansion of CD4+CD25+FOXP3+ regulatory T cells in infants of mothers with type 1 diabetes |
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