| Autor: |
Yan eSu, Ai-Hong eZhang, Nancy eNoben-Trauth, David William Scott |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
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| Zdroj: |
Frontiers in Microbiology, Vol 2 (2011) |
| Druh dokumentu: |
article |
| ISSN: |
1664-302X |
| DOI: |
10.3389/fmicb.2011.00154 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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