Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

• Published in: eLife Vol. 3
• Main Authors: Baptista, Antonio P, Roozendaal, Ramon, Reijmers, Rogier M, Koning, Jasper J, Unger, Wendy W, Greuter, Mascha, Keuning, Eelco D, Molenaar, Rosalie, Goverse, Gera, Sneeboer, Marlous M S, den Haan, Joke M M, Boes, Marianne, Mebius, Reina E
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 19.11.2014; eLife Sciences Publications, Ltd
• Subjects: Anergy; Antigen presentation; Antigens; Autoantigens; CD4 antigen; CD8 antigen; Cell growth; Clonal deletion; Dendritic cells; Experiments; Flow cytometry; Gene expression; Graft rejection; Immunity; Immunology; Immunoregulation; Lymph; lymph node stromal cell; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Major histocompatibility complex; MHC-II; Peptides; regulatory T cell; Software; Statistical analysis; Stromal cells; T cell receptors; Transplants & implants; Variance analysis; regulatory T cells; mouse; immunology; MHC-II; lymph node stromal cells
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.04433

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.