Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation
- Vrije Universiteit Medical Center, Netherlands
- Janssen Center of Excellence for Immunoprophylaxis, Netherlands
- University Medical Center Utrecht, Netherlands
Abstract
Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8+ T cells and MHC-II-dependent anergy of CD4+ T cells. Here, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of MHC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4+ as well as CD8+ T cells became activated, ultimately resulting in transplant rejection. MHC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.
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Ethics
Animal experimentation: All animal experiments were reviewed and approved by the Vrije University Scientific and Ethics Committees (protocols MCB09-35, MCB10-01 and MCB13-06). All surgery was performed under xylazine and ketamine anesthesia.
Copyright
© 2014, Baptista et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation
eLife 3:e04433.
https://doi.org/10.7554/eLife.04433
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