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Transfer of Central Nervous System Autoantigens and Presentation in Secondary Lymphoid Organs
- Source :
- Journal of immunology (Baltimore, Md., 169(10), 5415-5423. American Association of Immunologists
- Publication Year :
- 2002
- Publisher :
- The American Association of Immunologists, 2002.
-
Abstract
- Dendritic cells are thought to regulate tolerance induction vs immunization by transferring Ags and peripheral signals to draining lymph nodes (LN). However, whether myelin Ag transfer and presentation in LN occurs during demyelinating brain disease is unknown. In this study, we demonstrate redistribution of autoantigens from brain lesions to cervical LN in monkey experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Immunohistochemical analysis revealed significantly more cells containing myelin Ags in cervical LN of monkeys with EAE compared with those of healthy control monkeys. Myelin Ags were observed in cells expressing dendritic cell/macrophage-specific markers, MHC class II, and costimulatory molecules. Moreover, these cells were directly juxtaposed to T cells, suggesting that cognate interactions between myelin-containing APC and T cells are taking place in brain-draining LN. Indeed, myelin Ag-reactive T cells were observed in cervical LN from marmosets and rhesus monkeys. Importantly, these findings were paralleled by our findings in human tissue. We observed significantly more myelin Ag-containing cells in LN of individuals with MS compared with those of control individuals. These cells expressed APC markers, as observed in marmosets and rhesus monkeys. These findings suggest that during MS and EAE, modulation of T cell reactivity against brain-derived Ags also takes place in cervical LN and not necessarily inside the brain. A major implication is that novel therapeutic strategies may be targeted to peripheral events, thereby circumventing the blood-brain barrier.
- Subjects :
- Encephalomyelitis, Autoimmune, Experimental
Multiple Sclerosis
T-Lymphocytes
Encephalomyelitis
Immunology
Antigen presentation
Antigen-Presenting Cells
Epitopes, T-Lymphocyte
Inguinal Canal
Biology
Autoantigens
Myelin
medicine
Animals
Humans
Immunology and Allergy
Cell Aggregation
Antigen Presentation
MHC class II
Multiple sclerosis
Experimental autoimmune encephalomyelitis
Brain
Callithrix
Myelin Basic Protein
Dendritic cell
medicine.disease
Macaca mulatta
Macaca fascicularis
Protein Transport
Tolerance induction
medicine.anatomical_structure
Axilla
biology.protein
Lymph Nodes
Biomarkers
Neck
Spleen
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 169
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....59894bdf6d6e2bb79066cca56be6fb28