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Reprogrammed quiescent B cells provide an effective cellular therapy against chronic experimental autoimmune encephalomyelitis.
Eur J Immunol ; 41(6): 1696-708, 2011 Jun.
Article en En | MEDLINE | ID: mdl-21469107
Activated B cells can regulate immunity and have been envisaged as a potential cell-based therapy for treating autoimmune diseases. However, activated human B cells can also propagate immune responses, and the effects resulting from their infusion into patients cannot be predicted. This led us to consider resting B cells, which in contrast are poorly immunogenic, as an alternative cellular platform for the suppression of unwanted immunity. Here, we report that resting B cells can be directly engineered with lentiviral vectors to express antigens in a remarkably simple, rapid, and effective way. Notably, this neither required nor induced activation of the B cells. With this approach we were able to produce reprogrammed resting B cells that inhibited antigen-specific CD4(+) T cells, CD8(+) T cells, and B cells upon adoptive transfer in mice. Furthermore, resting B cells engineered to ectopically express myelin oligodendrocyte glycoprotein antigen protected recipient mice from severe disability and demyelination in EAE, and even induced complete remission from disease in mice lacking functional natural Tregs, which otherwise developed chronic paralysis. In conclusion, our study introduces reprogrammed quiescent B cells as a novel tool for suppressing undesirable immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Subgrupos de Linfocitos T / Linfocitos T Reguladores / Encefalomielitis Autoinmune Experimental / Tratamiento Basado en Trasplante de Células y Tejidos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Eur J Immunol Año: 2011 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Subgrupos de Linfocitos T / Linfocitos T Reguladores / Encefalomielitis Autoinmune Experimental / Tratamiento Basado en Trasplante de Células y Tejidos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Eur J Immunol Año: 2011 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania