Title |
Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease
|
---|---|
Published in |
Proceedings of the National Academy of Sciences of the United States of America, March 2016
|
DOI | 10.1073/pnas.1519608113 |
Pubmed ID | |
Authors |
Anne-Christine Flach, Tanja Litke, Judith Strauss, Michael Haberl, César Cordero Gómez, Markus Reindl, Albert Saiz, Hans-Jörg Fehling, Jürgen Wienands, Francesca Odoardi, Fred Lühder, Alexander Flügel |
Abstract |
Multiple sclerosis (MS) is caused by T cells that are reactive for brain antigens. In experimental autoimmune encephalomyelitis, the animal model for MS, myelin-reactive T cells initiate the autoimmune process when entering the nervous tissue and become reactivated upon local encounter of their cognate CNS antigen. Thereby, the strength of the T-cellular reactivation process within the CNS tissue is crucial for the manifestation and the severity of the clinical disease. Recently, B cells were found to participate in the pathogenesis of CNS autoimmunity, with several diverse underlying mechanisms being under discussion. We here report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. The antibodies accumulated in resident antigen-presenting phagocytes and significantly enhanced the activation of the incoming effector T cells. The ensuing strong blood-brain barrier disruption and immune cell recruitment resulted in rapid manifestation of clinical disease. Therefore, myelin oligodendrocyte glycoprotein (MOG)-specific autoantibodies can initiate disease bouts by cooperating with the autoreactive T cells in helping them to recognize their autoantigen and become efficiently reactivated within the immune-deprived nervous tissue. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 22% |
Korea, Republic of | 1 | 11% |
Canada | 1 | 11% |
Mexico | 1 | 11% |
Unknown | 4 | 44% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 7 | 78% |
Science communicators (journalists, bloggers, editors) | 1 | 11% |
Scientists | 1 | 11% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
United States | 1 | <1% |
Turkey | 1 | <1% |
France | 1 | <1% |
Unknown | 130 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 30 | 22% |
Researcher | 24 | 18% |
Student > Bachelor | 16 | 12% |
Student > Master | 11 | 8% |
Student > Doctoral Student | 10 | 7% |
Other | 21 | 16% |
Unknown | 22 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 24 | 18% |
Agricultural and Biological Sciences | 22 | 16% |
Medicine and Dentistry | 21 | 16% |
Neuroscience | 18 | 13% |
Biochemistry, Genetics and Molecular Biology | 12 | 9% |
Other | 11 | 8% |
Unknown | 26 | 19% |