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Tolerance induction by molecular mimicry: prevention and suppression of experimental autoimmune encephalomyelitis with the milk protein butyrophilin.
Int Immunol 2004; 16(3):489-99II

Abstract

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Although the etiology of MS remains unknown, studies in experimental autoimmune encephalomyelitis (EAE) have suggested that foreign molecules, which show molecular mimicry with myelin antigens, may play an important role as causative agents of the human disease. In this study, we investigate the molecular mimicry between the extracellular Ig-like domain of the cow's milk protein butyrophilin (BTN) and the extracellular domain of myelin oligodendrocyte glycoprotein (MOG), a candidate autoantigen in MS. Interestingly, we found that as a result of a non-pathogenic cross-reactivity that is localized to a subdominant region of MOG, treatment of C57BL/6 mice with BTN either before or after immunization with MOG was shown to prevent and also suppress the clinical manifestations of EAE. BTN treatment resulted in a significant reduction in both proliferation and production of Th1-related cytokines (IFN-gamma, IL-2, IL-12 and granulocyte macrophage colony stimulating factor) in response to MOG. This specific inhibition was consistently associated with an up-regulation in IL-10 secretion. Furthermore, adoptive transfer of BTN-specific T cells prior to active immunization with MOG resulted in a transitory reduction of the clinical symptoms. Our results suggest that the clinical improvement associated with BTN treatment involved the combination of both anergy and regulatory cells secreting high levels of IL-10. In conclusion, we show that despite the traditional link between molecular mimicry and pathogenic immune response, environmental agents that share homology with autoantigens may also represent a source of cells with a protective phenotype.

Authors+Show Affiliations

Department of Biochemistry, La Trobe University Bundoora, Victoria 3086, Australia. vaques@usc.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14978022

Citation

Mañá, Paula, et al. "Tolerance Induction By Molecular Mimicry: Prevention and Suppression of Experimental Autoimmune Encephalomyelitis With the Milk Protein Butyrophilin." International Immunology, vol. 16, no. 3, 2004, pp. 489-99.
Mañá P, Goodyear M, Bernard C, et al. Tolerance induction by molecular mimicry: prevention and suppression of experimental autoimmune encephalomyelitis with the milk protein butyrophilin. Int Immunol. 2004;16(3):489-99.
Mañá, P., Goodyear, M., Bernard, C., Tomioka, R., Freire-Garabal, M., & Liñares, D. (2004). Tolerance induction by molecular mimicry: prevention and suppression of experimental autoimmune encephalomyelitis with the milk protein butyrophilin. International Immunology, 16(3), pp. 489-99.
Mañá P, et al. Tolerance Induction By Molecular Mimicry: Prevention and Suppression of Experimental Autoimmune Encephalomyelitis With the Milk Protein Butyrophilin. Int Immunol. 2004;16(3):489-99. PubMed PMID: 14978022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tolerance induction by molecular mimicry: prevention and suppression of experimental autoimmune encephalomyelitis with the milk protein butyrophilin. AU - Mañá,Paula, AU - Goodyear,Melinda, AU - Bernard,Claude, AU - Tomioka,Ryo, AU - Freire-Garabal,Manuel, AU - Liñares,David, PY - 2004/2/24/pubmed PY - 2004/9/29/medline PY - 2004/2/24/entrez SP - 489 EP - 99 JF - International immunology JO - Int. Immunol. VL - 16 IS - 3 N2 - Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Although the etiology of MS remains unknown, studies in experimental autoimmune encephalomyelitis (EAE) have suggested that foreign molecules, which show molecular mimicry with myelin antigens, may play an important role as causative agents of the human disease. In this study, we investigate the molecular mimicry between the extracellular Ig-like domain of the cow's milk protein butyrophilin (BTN) and the extracellular domain of myelin oligodendrocyte glycoprotein (MOG), a candidate autoantigen in MS. Interestingly, we found that as a result of a non-pathogenic cross-reactivity that is localized to a subdominant region of MOG, treatment of C57BL/6 mice with BTN either before or after immunization with MOG was shown to prevent and also suppress the clinical manifestations of EAE. BTN treatment resulted in a significant reduction in both proliferation and production of Th1-related cytokines (IFN-gamma, IL-2, IL-12 and granulocyte macrophage colony stimulating factor) in response to MOG. This specific inhibition was consistently associated with an up-regulation in IL-10 secretion. Furthermore, adoptive transfer of BTN-specific T cells prior to active immunization with MOG resulted in a transitory reduction of the clinical symptoms. Our results suggest that the clinical improvement associated with BTN treatment involved the combination of both anergy and regulatory cells secreting high levels of IL-10. In conclusion, we show that despite the traditional link between molecular mimicry and pathogenic immune response, environmental agents that share homology with autoantigens may also represent a source of cells with a protective phenotype. SN - 0953-8178 UR - https://www.unboundmedicine.com/medline/citation/14978022/Tolerance_induction_by_molecular_mimicry:_prevention_and_suppression_of_experimental_autoimmune_encephalomyelitis_with_the_milk_protein_butyrophilin_ L2 - https://academic.oup.com/intimm/article-lookup/doi/10.1093/intimm/dxh049 DB - PRIME DP - Unbound Medicine ER -