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Chronologic localization of myelin-reactive cells in the lesions of relapsing EAE: implications for the study of
A H Cross1, T O'Mara, C S Raine
1Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461.
Abstract:
Although T cells play a pathogenetic role in MS, specific disease-inducing T cells have not been identified. T cells can be labeled and traced in adoptively transferred experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated animal model for MS. We have followed the appearance and topographic localization of radio-labeled myelin basic protein-reactive (MBP+) T cells in evolving lesions as EAE extended to other regions of the CNS. By high-resolution autoradiography, we confirmed that MBP+ cells initially homed to perivascular regions in the lower spinal cord. With increasing time after cell transfer, labeled cells appeared in more recent lesions in rostral locations (upper spinal cord, cerebellum, and forebrain) and constituted a progressively smaller percentage of cells in lower spinal cord lesions. The presence of unlabeled inflammatory cells in the CNS parenchyma coincided temporally with clinical signs. In agreement with previous studies, we have shown that MBP+ cells constituted a minority (mean, < 1.5%) of the total infiltrating cells and were most numerous in fresh lesions. We suggest that the perivascular regions of recent lesions would be the most likely areas to detect putative antigen-specific cells in MS lesions.
Insights
Researchers traced radio-labeled myelin basic protein-reactive T cells in an animal model for multiple sclerosis (MS). These specific T cells were found in early lesions, suggesting key areas for future MS research.
Area of Science:
- Neuroimmunology
- Cellular immunology
- Demyelinating diseases
Background:
- T cells are implicated in the pathology of multiple sclerosis (MS).
- Identifying specific disease-inducing T cells in MS remains a challenge.
- Experimental autoimmune encephalomyelitis (EAE) serves as a T-cell-mediated animal model for MS.
Purpose of the Study:
- To trace the migration and localization of myelin basic protein-reactive (MBP+) T cells within the central nervous system (CNS) during the progression of EAE.
- To understand the topographic distribution of antigen-specific T cells in evolving inflammatory lesions.
Main Methods:
- Adoptive transfer of radio-labeled MBP+ T cells into recipient mice with EAE.
- High-resolution autoradiography to track labeled cells in the CNS.
- Analysis of cell distribution in relation to lesion progression and clinical signs.
Main Results:
- Radio-labeled MBP+ T cells initially homed to perivascular regions in the lower spinal cord.
- Labeled cells appeared in more recent, rostral lesions over time.
- MBP+ cells constituted a small minority (<1.5%) of total infiltrating cells and were most abundant in fresh lesions.
Conclusions:
- Perivascular regions of recent lesions are the most probable sites to detect antigen-specific T cells in MS.
- The findings provide insights into the dynamics of T cell infiltration in autoimmune CNS inflammation.
- This study highlights the importance of antigen-specific T cell tracking in understanding MS pathogenesis.