期刊
IMMUNOLOGY LETTERS
卷 170, 期 -, 页码 52-63出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2016.01.002
关键词
B cells; Breg; Tfh; Th17; Costimulatory blockade; Transplantation tolerance
类别
资金
- NIH [AI41428, AI62765, AI72039]
- Department of Biotechnology, Government of India grants
- Ramalingaswami Fellowship [BT/03/IYBA/2010, BT/PR4610/MED/30/720/2012]
- German Research Foundation [HE3116/7-2]
- Council of Scientific and Industrial Research, Government of India
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.
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