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Oral administration of myelin basic protein is superior to myelin in suppressing established relapsing experimental autoimmune encephalomyelitis.
J Immunol. 1999 May 15; 162(10):6247-54.JI

Abstract

Oral administration of a myelin component, myelin basic protein (MBP), induces immunological unresponsiveness to CNS Ags and ameliorates murine relapsing experimental autoimmune encephalomyelitis (REAE). However, a recent clinical trial in which multiple sclerosis patients were treated with repeated doses of oral myelin was unsuccessful in reducing disease exacerbations. Therefore, we directly compared the tolerizing capacity of myelin vs MBP during REAE in B10.PL mice. Oral administration of high doses of myelin, either before disease induction or during REAE, did not provide protection from disease or decrease in vitro T cell responses. In contrast, repeated oral administration of high doses of MBP suppressed established disease and MBP-specific T cell proliferation and cytokine responses. The frequency of IL-2-, IFN-gamma-, and IL-5-secreting MBP-specific T cells declined with MBP feeding, implicating anergy and/or deletion as the mechanism(s) of oral tolerance after high Ag doses. We have previously shown that the dosage and timing of Ag administration are critical parameters in oral tolerance induction. Studies presented here demonstrate that Ag homogeneity is also important, i.e., homogeneous Ag (MBP) is more effective at inducing oral tolerance than heterogeneous Ag (myelin).

Authors+Show Affiliations

Department of Medical Microbiology and Immunology, Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10229871

Citation

Benson, J M., et al. "Oral Administration of Myelin Basic Protein Is Superior to Myelin in Suppressing Established Relapsing Experimental Autoimmune Encephalomyelitis." Journal of Immunology (Baltimore, Md. : 1950), vol. 162, no. 10, 1999, pp. 6247-54.
Benson JM, Stuckman SS, Cox KL, et al. Oral administration of myelin basic protein is superior to myelin in suppressing established relapsing experimental autoimmune encephalomyelitis. J Immunol. 1999;162(10):6247-54.
Benson, J. M., Stuckman, S. S., Cox, K. L., Wardrop, R. M., Gienapp, I. E., Cross, A. H., Trotter, J. L., & Whitacre, C. C. (1999). Oral administration of myelin basic protein is superior to myelin in suppressing established relapsing experimental autoimmune encephalomyelitis. Journal of Immunology (Baltimore, Md. : 1950), 162(10), 6247-54.
Benson JM, et al. Oral Administration of Myelin Basic Protein Is Superior to Myelin in Suppressing Established Relapsing Experimental Autoimmune Encephalomyelitis. J Immunol. 1999 May 15;162(10):6247-54. PubMed PMID: 10229871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral administration of myelin basic protein is superior to myelin in suppressing established relapsing experimental autoimmune encephalomyelitis. AU - Benson,J M, AU - Stuckman,S S, AU - Cox,K L, AU - Wardrop,R M, AU - Gienapp,I E, AU - Cross,A H, AU - Trotter,J L, AU - Whitacre,C C, PY - 1999/5/7/pubmed PY - 1999/5/7/medline PY - 1999/5/7/entrez SP - 6247 EP - 54 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 162 IS - 10 N2 - Oral administration of a myelin component, myelin basic protein (MBP), induces immunological unresponsiveness to CNS Ags and ameliorates murine relapsing experimental autoimmune encephalomyelitis (REAE). However, a recent clinical trial in which multiple sclerosis patients were treated with repeated doses of oral myelin was unsuccessful in reducing disease exacerbations. Therefore, we directly compared the tolerizing capacity of myelin vs MBP during REAE in B10.PL mice. Oral administration of high doses of myelin, either before disease induction or during REAE, did not provide protection from disease or decrease in vitro T cell responses. In contrast, repeated oral administration of high doses of MBP suppressed established disease and MBP-specific T cell proliferation and cytokine responses. The frequency of IL-2-, IFN-gamma-, and IL-5-secreting MBP-specific T cells declined with MBP feeding, implicating anergy and/or deletion as the mechanism(s) of oral tolerance after high Ag doses. We have previously shown that the dosage and timing of Ag administration are critical parameters in oral tolerance induction. Studies presented here demonstrate that Ag homogeneity is also important, i.e., homogeneous Ag (MBP) is more effective at inducing oral tolerance than heterogeneous Ag (myelin). SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10229871/Oral_administration_of_myelin_basic_protein_is_superior_to_myelin_in_suppressing_established_relapsing_experimental_autoimmune_encephalomyelitis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10229871 DB - PRIME DP - Unbound Medicine ER -