Lal, Girdhari and Kulkarni, Neeraja and Nakayama, Yumi and Singh, Amit K. and Sethi, Apoorva and Burrell, Bryna E. and Brinkman, C. Colin and Iwami, Daiki and Zhang, Tianshu and Hehlgans, Thomas and Bromberg, Jonathan S. (2016) IL-10 from marginal zone precursor B cells controls the differentiation of Th17, Tfh and Tfr cells in transplantation tolerance. IMMUNOLOGY LETTERS, 170. pp. 52-63. ISSN 0165-2478, 1879-0542
Full text not available from this repository. (Request a copy)Abstract
B cells are known to control CD4T cell differentiation in secondary lymphoid tissues. We hypothesized that IL-10 expression by marginal zone precursor (MZP) regulatory B cells controls the differentiation and positioning of effector and regulatory T cells during tolerization. Costimulatory blockade with donor specific transfusion (DST) and anti-CD4OL mAb in C57BL/6 mice induced tolerance to allogeneic cardiac allograft. B cell depletion or IL-10 deficiency in B cells prevented tolerance, resulting in decreased follicular regulatory CD4(+) T cells (Tfr) and increased IL-21 expression by T follicular helper (Tfh) cells in the B cell and T cell zones. IL-21 acted with IL-6 to induce CCR6(+) Th17 that caused rejection. Deficiency or blockade of IL-6, IL-21, IL-21R, or CCR6 prevented B cell depletion-induced acute cellular rejection; while agonistic mCCL20-Ig induced rejection. Adoptive transfer of IL-10(+/+) MZP in tolerogen treated CD19-Cre(+/-):IL-10(fl/fl) mice rescued the localization of Tfh and Tfr cells in the B cell follicle and prevented allograft rejection. MZP B cell IL-10 is necessary for tolerance and controls the differentiation and position of Th17, Tfh and Tfr cells in secondary lymphoid tissues. This has implications for understanding tolerance induction and how B cell depletion may prevent tolerance. (C) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COSTIMULATION BLOCKADE; ALLOGRAFT-REJECTION; ANTIBODY-RESPONSES; IL-21; INTERLEUKIN-21; INDUCTION; DISEASE; MICE; B cells; Breg; Tfh; Th17; Costimulatory blockade; Transplantation tolerance |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Mar 2019 07:02 |
| Last Modified: | 14 Mar 2019 07:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2453 |
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