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Aire deficient mice develop multiple features of APECED phenotype and show altered immune response

2002; Oxford University Press; Volume: 11; Issue: 4 Linguagem: Inglês

10.1093/hmg/11.4.397

1460-2083

Chris Ramsey, Ola Winqvist, Lea Puhakka, Maria Halonen, Aune Moro, Olle Kämpe, Petra Eskelin, Markku Pelto‐Huikko, Leena Peltonen,

Diabetes and associated disorders

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autosomal recessive disease caused by mutations in the AIRE gene. Here we have produced knock-out mice for the Aire gene. The Aire–/– mice develop normally; however, autoimmune features of APECED in Aire–/– mice are evident, including multiorgan lymphocytic infiltration, circulating autoantibodies and infertility. The distribution of B and T cells and thymic maturation as well as activation of T cells appear normal, while the TCR-Vβ repertoire is altered in peripheral T cells of Aire–/– mice. When mice are challenged with immunization, the peripheral T cells of Aire–/– mice have a 3–5-fold increased proliferation. These findings suggest that the Aire gene is not necessary for normal T cell education and development, while a defect in immune response detected in challenged Aire–/– mice underlines the crucial role of AIRE/Aire in maintaining homeostatic regulation in the immune system.