B-cell gene therapy for tolerance induction: host but not donor B cell derived IL-10 is necessary for tolerance

Frontiers in Microbiology

Yan eSu²  Ai-Hong eZhang²  David William Scott²  Nancy eNoben-Trauth³ 

[1] Uniformed Services University of Health Sciences ;University of Maryland School of Medicine;University of Maryland at Shady Groove Center;

关键词: Gene Therapy;    tolerance;    IL-10;    B cells;    IL-10 receptor;   

DOI  :  10.3389/fmicb.2011.00154

来源: DOAJ

【 摘 要 】

Genetically modified B cells are excellent tolerogenic APCs in multiple models of autoimmunity. However, the mechanisms of action are still not completely understood. In our models, we generate antigen-specific tolerogenic B cells by transducing naïve or primed B cells with an antigen-immunoglobulin G (peptide-IgG) construct. In order to be transduced, B cells require activation with mitogens such as LPS. We and others have found that LPS stimulation of B cells upregulates the production of IL-10, a key cytokine for maintaining immune tolerance. In the current study, we defined the role of B-cell produced IL-10 in tolerance induction by using IL-10 deficient B cells as donor APCs. We found that peptide-IgG transduced IL-10 KO B cells have the same effects as wt B cells in tolerance induction in an EAE model. Moreover, we demonstrated that the tolerogenic effect of peptide-IgG B cells was completely abrogated in anti-IL-10 receptor antibody treated recipients. Taken together, our results suggest that tolerance induced by peptide-IgG B-cell gene therapy requires IL-10 from the host but not donor B cells.These data shed important insights into the mechanisms of tolerance induction mediated by B-cell gene therapy.

【 授权许可】

Unknown