Oral tolerance as therapy for experimental autoimmune encephalomyelitis and multiple sclerosis: demonstration of T cell anergy

Immunology and Cell Biology
S D JewellC C Whitacre

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an important model for developing therapies for multiple sclerosis (MS). The oral administration of the central nervous system antigen, myelin basic protein (MBP), to Lewis rats and susceptible mouse strains prior to MBP immunization prevents the induction of EAE. Clinical trials administering myelin orally to MS patients have met with only partial success, and thus require that oral tolerance be further studied to improve this treatment strategy. Clonal anergy, clonal deletion, immune deviation from Th1 to Th2 T cell subsets, and active suppression by TGF-beta-secreting T cells have all been implicated as possible mechanisms in oral tolerance. Which mechanism predominates depends on antigen dosage, frequency of feeding, and timing of antigen administration. In this study, we have characterized T cells derived from MBP-fed rats and determined the level of their unresponsiveness. Myelin basic protein-specific T cells are indeed present although in reduced numbers in lymphoid tissue of orally tolerized animals. Following several cell divisions in the presence of IL-2, these MBP-specific T cells undergo a dramatic reversal of unresponsiveness, proliferate in response to MBP and ar...Continue Reading

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Citations

May 20, 1998·Research in Immunology·J M Benson, C C Whitacre
Apr 29, 1998·Immunology and Cell Biology·D O Willenborg, M A Staykova
Apr 3, 2004·Arthritis Research & Therapy·N Fredrik Bäckström, Ulf I H Dahlgren
Oct 27, 2004·Journal of Autoimmunity·Patricia A GonnellaHoward L Weiner
Mar 26, 2004·Human Immunology·Melanie L MolitorWilliam J Burlingham
Nov 8, 2006·Current Opinion in Allergy and Clinical Immunology·Takachika Hiroi, Fumio Takaiwa
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Richard E JonesDennis Bourdette
Aug 8, 2018·Chinese Medical Journal·Ruo-Yang FengHua Yan

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