TY  - JOUR
A1  - Honke, Nadine
A1  - Shaabani, Namir
A1  - Teijaro, John R.
A1  - Christen, Urs
A1  - Hardt, Cornelia
A1  - Bezgovsek, Judith
A1  - Lang, Philipp A.
A1  - Lang, Karl S.
T1  - Presentation of autoantigen in peripheral lymph nodes is sufficient for priming autoreactive CD8+ T cells
T2  - Frontiers in Immunology.
N2  - Peripheral tolerance is an important mechanism by which the immune system can guarantee a second line of defense against autoreactive T and B cells. One autoimmune disease that is related to a break of peripheral tolerance is diabetes mellitus type 1. Using the RIP-GP mouse model, we analyzed the role of the spleen and lymph nodes (LNs) in priming CD8+ T cells and breaking peripheral tolerance. We found that diabetes developed in splenectomized mice infected with the lymphocytic choriomeningitis virus (LCMV), a finding showing that the spleen was not necessary in generating autoimmunity. By contrast, the absence of LNs prevented the priming of LCMV-specific CD8+ T cells, and diabetes did not develop in these mice. Additionally, we found that dendritic cells are responsible for the distribution of virus in secondary lymphoid organs, when LCMV was administered intravenously. Preventing this distribution with the sphingosine-1-phosphate receptor antagonist FTY720 inhibits the transport of antigen to peripheral LNs and consequently prevented the onset of diabetes. However, in case of subcutaneous infection, administration of FTY720 could not inhibit the onset of diabetes because the viral antigen is already presented in the peripheral LNs. These findings demonstrate the importance of preventing the presence of antigen in LNs for maintaining tolerance.
KW  - autoimmune diabetes
KW  - lymph nodes
KW  - LCMV
KW  - enforced viral replication
KW  - sphingosine-1-phosphate receptor
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/42922
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-429229
N1  - Copyright: © 2017 Honke, Shaabani, Teijaro, Christen, Hardt, Bezgovsek, Lang and Lang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) http://creativecommons.org/licenses/by/4.0/ . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 8
IS  - Article 113
SP  - 1
EP  - 11
ER  -