Article ; Online: Antigen clearance at the peak of the primary immune response induces experimental autoimmune encephalomyelitis.
European journal of immunology
2023 Volume 53, Issue 3, Page(s) e2250122
Abstract: Autoimmune demyelinating diseases can be induced by an immune response against myelin peptides; however, the exact mechanism underlying the development of such diseases remains unclear. In experimental autoimmune encephalomyelitis, we found that the ... ...
| Abstract | Autoimmune demyelinating diseases can be induced by an immune response against myelin peptides; however, the exact mechanism underlying the development of such diseases remains unclear. In experimental autoimmune encephalomyelitis, we found that the clearance of exogenous myelin antigen at the peak of the primary immune response is key to the pathogenesis of the disease. The generation of effector T cells requires continuous antigen stimulation, whereas redundant antigen traps and exhausts effector T cells in the periphery, which induces resistance to the disease. Moreover, insufficient antigenic stimulation fails to induce disease efficiently owing to insufficient numbers of effector T cells. When myelin antigen is entirely cleared, the number of effector T cells reaches a peak, which facilitates infiltration of more effector T cells into the central nervous system. The peripheral antigen clearance initiates the first wave of effector T cell entry into the central nervous system and induces chronic inflammation. The inflamed central nervous system recruits the second wave of effector T cells that worsen inflammation, resulting in loss of self-tolerance. These findings provide new insights into the mechanism underlying the development of autoimmune demyelinating diseases, which may potentially impact future treatments. |
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| MeSH term(s) | Animals ; Encephalomyelitis, Autoimmune, Experimental ; T-Lymphocytes ; Central Nervous System/pathology ; Inflammation ; Immunity |
| Language | English |
| Publishing date | 2023-01-19 |
| Publishing country | Germany |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 120108-6 |
| ISSN | 1521-4141 ; 0014-2980 |
| ISSN (online) | 1521-4141 |
| ISSN | 0014-2980 |
| DOI | 10.1002/eji.202250122 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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