| First Author | Rouhani SJ | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6771 | PubMed ID | 25857745 |
| Mgi Jnum | J:222732 | Mgi Id | MGI:5645437 |
| Doi | 10.1038/ncomms7771 | Citation | Rouhani SJ, et al. (2015) Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction. Nat Commun 6:6771 |
| abstractText | Lymphatic endothelial cells (LECs) directly express peripheral tissue antigens and induce CD8 T-cell deletional tolerance. LECs express MHC-II molecules, suggesting they might also tolerize CD4 T cells. We demonstrate that when beta-galactosidase (beta-gal) is expressed in LECs, beta-gal-specific CD8 T cells undergo deletion via the PD-1/PD-L1 and LAG-3/MHC-II pathways. In contrast, LECs do not present endogenous beta-gal in the context of MHC-II molecules to beta-gal-specific CD4 T cells. Lack of presentation is independent of antigen localization, as membrane-bound haemagglutinin and I-Ealpha are also not presented by MHC-II molecules. LECs express invariant chain and cathepsin L, but not H2-M, suggesting that they cannot load endogenous antigenic peptides onto MHC-II molecules. Importantly, LECs transfer beta-gal to dendritic cells, which subsequently present it to induce CD4 T-cell anergy. Therefore, LECs serve as an antigen reservoir for CD4 T-cell tolerance, and MHC-II molecules on LECs are used to induce CD8 T-cell tolerance via LAG-3. |
