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Fast Progression of Recombinant Human Myelin/Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis in Marmosets Is Associated with the Activation of MOG34–56-Specific Cytotoxic T Cells
| Content Provider | Scilit |
|---|---|
| Author | Kap, Yolanda S. Smith, Paul Jagessar, S. Anwar Remarque, Ed Blezer, Erwin Strijkers, Gustav J. Laman, Jon D. Hintzen, Rogier Q. Bauer, Jan Brok, Herbert P. M. Hart, Bert A. ‘T |
| Copyright Year | 2008 |
| Description | The recombinant human (rh) myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) model in the common marmoset is characterized by 100% disease incidence, a chronic disease course, and a variable time interval between immunization and neurological impairment. We investigated whether monkeys with fast and slow disease progression display different anti-MOG T or B cell responses and analyzed the underlying pathogenic mechanism(s). The results show that fast progressor monkeys display a significantly wider specificity diversification of anti-MOG T cells at necropsy than slow progressors, especially against $MOG_{34–56}$ and $MOG_{74–96}$. $MOG_{34–56}$ emerged as a critical encephalitogenic peptide, inducing severe neurological disease and multiple lesions with inflammation, demyelination, and axonal injury in the CNS. Although EAE was not observed in $MOG_{74–96}$-immunized monkeys, weak T cell responses against $MOG_{34–56}$ and low grade CNS pathology were detected. When these cases received a booster immunization with $MOG_{34–56}$ in IFA, full-blown EAE developed. $MOG_{34–56}$-reactive T cells expressed CD3, CD4, or CD8 and CD56, but not CD16. Moreover, $MOG_{34–56}$-specific T cell lines displayed specific cytotoxic activity against peptide-pulsed B cell lines. The phenotype and cytotoxic activity suggest that these cells are NK-CTL. These results support the concept that cytotoxic cells may play a role in the pathogenesis of multiple sclerosis. |
| Ending Page | 1337 |
| Page Count | 12 |
| Starting Page | 1326 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.180.3.1326 |
| Journal | The Journal of Immunology |
| Issue Number | 3 |
| Volume Number | 180 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2008-02-01 |
| Access Restriction | Open |
| Subject Keyword | Specific Cytotoxic Cell Responses Cytotoxic T Cells 34â |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
