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Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis.
- Source :
-
Journal of autoimmunity [J Autoimmun] 2010 Aug; Vol. 35 (1), pp. 33-44. Date of Electronic Publication: 2010 Feb 20. - Publication Year :
- 2010
-
Abstract
- Immune-based self-recognition and failure to modulate this response are believed to contribute to the debilitating autoimmune pathology observed in multiple sclerosis (MS). Studies from its murine model, experimental autoimmune encephalomyelitis (EAE), have shown that neuroantigen-specific CD4+T cells are capable of inducing disease, while their immune sibling, the CD8+T cells, have largely been ignored. To understand their role in autoimmune demyelination, we first confirmed that, similar to our observations in human MS, there is robust induction of neuroantigen-reactive CD8+T cells in several models, including MOG(35-55)/CFA-induced EAE. However, MOG(35-55)-specific CD8+T-cells, when purified, were unable to adoptively transfer disease into naïve mice (in contrast to CD4+T-cells). In fact, we observed that the transfer of these neuroantigen-specific CD8+T cells was able to suppress the induction of EAE and to inhibit ongoing EAE. These regulatory CD8+T cells produced IFN-gamma and perforin and were able to kill MOG loaded CD4+T-cells as well as CD4-depleted APC, suggesting a cytotoxic/suppressor mechanism. Inhibition of EAE was associated with both the modulation of APC function as well as decreased MOG-specific CD4+T cell responses. Our studies reveal a novel and unexpected immune regulatory function for neuroantigen-specific CD8+T cells and have interesting biologic and therapeutic implications.
- Subjects :
- Animals
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes pathology
Cells, Cultured
Cytotoxicity, Immunologic
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental pathology
Female
Glycoproteins immunology
Humans
Interferon-gamma metabolism
Mice
Mice, Inbred C57BL
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments immunology
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory pathology
CD8-Positive T-Lymphocytes metabolism
Central Nervous System immunology
Encephalomyelitis, Autoimmune, Experimental immunology
Multiple Sclerosis immunology
T-Lymphocytes, Regulatory metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9157
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 20172692
- Full Text :
- https://doi.org/10.1016/j.jaut.2010.01.003