In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis

J. Jeremiah Bell, Rohit D. Divekar, Jason S. Ellis, Jason A. Cascio, Cara L. Haymaker, Renu Jain, Danielle Tartar, Christine M. Hoeman, John C. Hardaway, Habib Zaghouani

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3 Scopus citations

Abstract

A number of Ag-specific approaches have been developed that ameliorate experimental allergic encephalomyelitis (EAE), an animal model for the human autoimmune disease multiple sclerosis. Translation to humans, however, remains a consideration, justifying the search for more insight into the mechanism underlying restoration of self-tolerance. Ig-proteolipid protein (PLP) 1 and Ig-myelin oligodendrocyte glycoprotein (MOG) are Ig chimeras carrying the encephalitogenic PLP 139-151 and MOG 35-55 amino acid sequence, respectively. Ig-PLP1 ameliorates EAE in SJL/J (H-2s) mice while Ig-MOG modulates the disease in C57BL/6 (H-2b) animals. In this study, we asked whether the chimeras would suppress EAE in F1 mice expressing both parental MHC alleles and representing a polymorphism with more relevance to human circumstances. The results show that Ig-MOG modulates both PLP1 and MOG peptide-induced EAE in the F1 mice, whereas Ig-PLP1 counters PLP1 EAE but exacerbates MOG-induced disease. This in trans aggravation of MOG EAE by Ig-PLP1 operates through induction of PLP1-specific T cells producing IL-5 that sustained inhibition of MOG-specific Abs leading to exacerbation of EAE. Thus, in trans T cell tolerance, which should be operative in polymorphic systems, can aggravate rather than ameliorate autoimmunity. This phenomenon possibly takes place through interference with protective humoral immunity.

Original languageEnglish (US)
Pages (from-to)1508-1516
Number of pages9
JournalJournal of Immunology
Volume180
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Bell, J. J., Divekar, R. D., Ellis, J. S., Cascio, J. A., Haymaker, C. L., Jain, R., Tartar, D., Hoeman, C. M., Hardaway, J. C., & Zaghouani, H. (2008). In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis. Journal of Immunology, 180(3), 1508-1516. https://doi.org/10.4049/jimmunol.180.3.1508