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

Roy, Edwige; Leduc, Michèle; Guégan, Sarah; Rachdi, Latif; Kluger, Nicolas; Scharfmann, Raphaël; Aractingi, S.; Khosrotehrani, Kiarash

doi:10.1016/j.jaut.2011.02.003

Cited by 32 publications

(22 citation statements)

References 46 publications

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“…The cell types exchanged between mother and fetus include leukocytes and T cells [268][269][270][271] in addition to progenitors of different line-ages [267,272], such as hematopoietic [267] or mesenchymal stem cells [273] and/or endothelial progenitors [274]. It was suggested that maternal T and potentially B cells transferred during pregnancy or lactation might play a role in the development of T1DM [275].…”

Section: Diabeticsmentioning

confidence: 99%

“…Roy et al [275] believe that fetal microchimeric cells did not seem to influence the level of islet inflammation in mothers despite their antibeta cell specificity. They showed that fetal lymphoid progenitor cells enter the maternal thymus and develop into double positive and single positive thymocyte [270].…”

Section: Diabeticsmentioning

confidence: 99%

“…Given the absence of activity of autoantibodies in this process [330,331], it seems that maternal T and predominantly B cells transferred during gestation or lactation might play a role in development of autoimmune diabetes. Roy et al [275] found that in mice maternal T cells reactive against the endocrine pancreas of their progeny markedly increased islet infiltration. Specific maternal microchimeric T cells targeting fetal antigens in beta cells may also constitute evidence of their predisposing role in development of autoimmune T1DM.…”

Section: Parametersmentioning

confidence: 99%

See 2 more Smart Citations

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

Pr¹,

ota²

2013

J Diabetes Metab

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Recently, it was suggested that maternal T and potentially B cells transferred during pregnancy and/or the breast milk feeding and their encounter with the antigen in mesenteric lymph nodes might play a role in development of type 1 diabetes mellitus (T1DM). T. gondii infection during gestation and/or after birth may be responsible for development of both T1DM and T2DM in children, adolescents and adults because: a) maternal microchimerism in peripheral blood was demonstrated to be significantly higher in patients with T1DM compared to unaffected siblings and healthy subjects, b) transmission of T. gondii as a Trojan horse in various types of eukaryotic cells, including T and B lymphocytes, c) swallowing by the fetus of amniotic fluid containing infected leukocytes and other cells, d) elimination of T. gondii in the breast milk during lactation, e) involvement of mesenteric lymph nodes after oral infection with the parasite, and f) damage of the myenteric neurons during infection with the parasite in both the animals with streptozotocin-induced diabetes and diabetic patients. Moreover, a significantly lower occurrence of antibodies against T. gondii found in the sera of patients with T1DM compared with their first-degree family members or healthy controls may be due to their T and/or B cell exhaustion perspective caused by chronic infection with the parasite. This suggestion may be supported by the finding that latent toxoplasmosis was associated with markedly reduced lymphocyte B-cell counts responsible for production of antibodies, markedly lower serum IgG, IgM, and IgA levels, and a significant suppression of IL-2. On the other hand, patients with T2DM had increased anti-T. gondii antibodies significantly more frequently than respective controls. Impaired vascular endothelial function characteristic for the patients with diabetes mellitus may be at least in part due to the preferential T. gondii infection of endothelial cells. Vitamin D and minocycline exerted beneficial effects on development and clinical course of diabetes mellitus probably because of their immunomodulatory and antitoxoplasmatic activities. These data strongly suggest that the parasite play an important role in development of both types of diabetes mellitus.

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Section: Diabeticsmentioning

confidence: 99%

Section: Diabeticsmentioning

confidence: 99%

Section: Parametersmentioning

confidence: 99%

See 1 more Smart Citation

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

Pr¹,

ota²

2013

J Diabetes Metab

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“…65 We examined RIP-OVA transgenic mice expressing low levels of ovalbumin in pancreatic β cells. These mice, when injected with high numbers of activated anti-ovalbumin T cells such as OT2 T cells, develop islet inflammation.…”

Section: Maternal Microchimeric T Cells May Initiate a Fetal Autoimmumentioning

confidence: 99%

Can maternal microchimeric cells influence the fetal response toward self antigens?

Lévêque

Khosrotehrani

2011

Chimerism

Self Cite

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“…23,24 The accumulation of apoptotic β cells with defective clearance could lead to cell necrosis thus activating the immune system. Perhaps maternal islet autoantigens released by dying β cells could initiate an immune response which is later shifted to autoimmunity, as demonstrated in a murine model of microchimerism by Roy E et al 25 Alternatively, islet autoantigens presented on maternal antigen presenting cells (APCs) could prime host T cells. A recent study suggested that the antigen presenting capacity of cord blood naïve monocytes was reduced due to low expression of molecules involved in presentation and co-stimulation but normalized after 8 months of age when islet autoimmunity appears.…”

mentioning

confidence: 99%

Maternal microchimerism

Vives-Pi

Gillespie

2014

Chimerism

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

Cited by 32 publications

References 46 publications

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

Can maternal microchimeric cells influence the fetal response toward self antigens?

Maternal microchimerism

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