Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation
Antonio P Baptista,
Ramon Roozendaal,
Rogier M Reijmers,
Jasper J Koning,
Wendy W Unger,
Mascha Greuter,
Eelco D Keuning,
Rosalie Molenaar,
Gera Goverse,
Marlous M S Sneeboer,
Joke M M den Haan,
Marianne Boes,
Reina E Mebius
Affiliations
Antonio P Baptista
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands; Graduate Program in Areas of Basic and Applied Biology, University of Porto, Porto, Portugal
Ramon Roozendaal
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Rogier M Reijmers
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Jasper J Koning
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Wendy W Unger
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Mascha Greuter
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Eelco D Keuning
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Rosalie Molenaar
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Gera Goverse
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Marlous M S Sneeboer
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Joke M M den Haan
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
Marianne Boes
Department of Pediatric Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
Reina E Mebius
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands
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. In this study, 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.