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The third signal in T cell-mediated autoimmune disease?
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Jul 01; Vol. 173 (1), pp. 92-9. - Publication Year :
- 2004
-
Abstract
- The initial event in the pathogenesis of autoimmune disease is thought to be the priming of naive autoreactive T cells by an infection with a cross-reactive microorganism. Although such cross-reactive priming should be a common event, autoimmune disease does not frequently develop. This situation is reflected after the immunization of C57BL/6 mice with the neuroantigen myelin oligodendrocyte glycoprotein (MOG) with CFA, which primes a type 1 T cell response but does not lead to clinical or histological manifestation of experimental allergic encephalomyelitis unless pertussis toxin is injected in addition. We show in this study that, in MOG:CFA-primed mice, the autoimmune CNS pathology develops after intracerebral deposition of TLR9-activating CpG oligonucleotides, but not following non-CpG oligonucleotide injection or after aseptic cryoinjury of the brain. Thus, access of primed MOG-specific Th1 cells to the uninflamed CNS or to CNS undergoing sterile inflammation did not suffice to elicit autoimmune pathology; only if the APC in the target organ were activated in addition by the TLR9-stimulating microbial product did they exert local effector functions. The data suggest that such licensing of APC in the target organ by microbial stimuli represents a checkpoint for functional self-tolerance. Therefore, microorganisms unrelated to the cross-reactive agent that primes the autoreactive T cells could dictate the onset and exacerbation of autoimmune diseases.
- Subjects :
- Animals
Antigen-Presenting Cells physiology
Autoantigens immunology
Brain immunology
CD40 Antigens biosynthesis
Chemokines biosynthesis
DNA-Binding Proteins physiology
Female
Immune Tolerance
Immunization
Mice
Mice, Inbred C57BL
Myelin Proteins
Myelin-Associated Glycoprotein immunology
Myelin-Oligodendrocyte Glycoprotein
Oligodeoxyribonucleotides pharmacology
Receptors, Cell Surface physiology
Toll-Like Receptor 9
Autoimmune Diseases etiology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 173
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15210763
- Full Text :
- https://doi.org/10.4049/jimmunol.173.1.92