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IL-10 diminishes CTLA-4 expression on islet-resident T cells and sustains their activation rather than tolerance.
Gregg, Randal K; Bell, J Jeremiah; Lee, Hyun-Hee; Jain, Renu; Schoenleber, Scott J; Divekar, Rohit; Zaghouani, Habib.
Afiliación
  • Gregg RK; Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
J Immunol ; 174(2): 662-70, 2005 Jan 15.
Article en En | MEDLINE | ID: mdl-15634884
IL-10, a powerful anti-Th1 cytokine, has shown paradoxical effects against diabetes. The mechanism underlying such variable function remains largely undefined. An approach for controlled mobilization of endogenous IL-10 was applied to the NOD mouse and indicated that IL-10 encounter with diabetogenic T cells within the islets sustains activation, while encounter occurring peripheral to the islets induces tolerance. Insulin beta-chain (INSbeta) 9-23 peptide was expressed on an Ig, and the aggregated (agg) form of the resulting Ig-INSbeta triggered IL-10 production by APCs, and expanded IL-10-producing T regulatory cells. Consequently, agg Ig-INSbeta delayed diabetes effectively in young NOD mice whose pathogenic T cells remain peripheral to the islets. However, agg Ig-INSbeta was unable to suppress the disease in 10-wk-old insulitis-positive animals whose diabetogenic T cells have populated the islets. This is not due to irreversibility of the disease because soluble Ig-INSbeta did delay diabetes in these older mice. Evidence is provided indicating that upon migration to the islet, T cells were activated and up-regulated CTLA-4 expression. IL-10, however, reverses such up-regulation, abolishing CTLA-4-inhibitory functions and sustaining activation of the islet T lymphocytes. Therefore, IL-10 supports T cell tolerance in the periphery, but its interplay with CTLA-4 sustains activation within the islets. As a result, IL-10 displays opposite functions against diabetes in young vs older insulitis-positive mice.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Antígenos de Diferenciación / Regulación hacia Abajo / Subgrupos de Linfocitos T / Islotes Pancreáticos / Interleucina-10 / Diabetes Mellitus Tipo 1 / Tolerancia Inmunológica Límite: Animals Idioma: En Revista: J Immunol Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Buscar en Google
Añadir a Mi BVS
Imprimir
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PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Antígenos de Diferenciación / Regulación hacia Abajo / Subgrupos de Linfocitos T / Islotes Pancreáticos / Interleucina-10 / Diabetes Mellitus Tipo 1 / Tolerancia Inmunológica Límite: Animals Idioma: En Revista: J Immunol Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos