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Effect of timing of intravenous administration of myelin basic protein on the induction of tolerance in experimental allergic encephalomyelitis.
Mult Scler. 1999 Feb; 5(1):2-9.MS

Abstract

Immunological tolerance and suppression of clinical and histological experimental allergic encaphalomyelitis (EAE) can be induced by the intravenous (i.v.) administration of myelin basic protein (MBP). In this report we have characterized the effect of the time of i.v. administration of MBP on the course of EAE in Lewis rats. Rats were treated with the i.v. administration of one or two 500 micrograms doses of MBP either before or after active immunization. Results indicated that i.v. administration of MBP in rats before active immunization with MBP/CFA (naïve rats) was most effective when given 14 days before active immunization, but treatment of rats actively immunized with MBP (immunized rats) was most effective at the onset of disease. Treatment at other times was less effective. The i.v. administration of the peptide MBP 68-88 (p68-88) containing the dominant encephalitogenic epitope could also suppress MBP-induced EAE in a dose dependent manner. Intravenous administration of two injections of p68-88 to naïve rats on days 10 and 3 before, or on days 0 and 7 after, active immunization with MBP suppressed the development of EAE in a dose dependent manner. Treatment of rats with i.v. MBP after, but not before, the transfer of MBP-reactive EAE effector cells suppressed the development of EAE in the recipient rats. Transfer of lymphoid cells from tolerized naïve rats failed to protect recipient rats against development of active or passive EAE. These results indicate the importance of timing and dose of the antigen on the induction of tolerance and suggests different mechanisms of tolerance induction by intravenous MBP in immunized and naïve rats. They also emphasize the importance of timing in designing efficient treatment strategies when i.v. tolerance is contemplated in EAE and possibly multiple sclerosis.

Authors+Show Affiliations

Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10096096

Citation

Hilliard, B, et al. "Effect of Timing of Intravenous Administration of Myelin Basic Protein On the Induction of Tolerance in Experimental Allergic Encephalomyelitis." Multiple Sclerosis (Houndmills, Basingstoke, England), vol. 5, no. 1, 1999, pp. 2-9.
Hilliard B, Ventura ES, Rostami A. Effect of timing of intravenous administration of myelin basic protein on the induction of tolerance in experimental allergic encephalomyelitis. Mult Scler. 1999;5(1):2-9.
Hilliard, B., Ventura, E. S., & Rostami, A. (1999). Effect of timing of intravenous administration of myelin basic protein on the induction of tolerance in experimental allergic encephalomyelitis. Multiple Sclerosis (Houndmills, Basingstoke, England), 5(1), 2-9.
Hilliard B, Ventura ES, Rostami A. Effect of Timing of Intravenous Administration of Myelin Basic Protein On the Induction of Tolerance in Experimental Allergic Encephalomyelitis. Mult Scler. 1999;5(1):2-9. PubMed PMID: 10096096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of timing of intravenous administration of myelin basic protein on the induction of tolerance in experimental allergic encephalomyelitis. AU - Hilliard,B, AU - Ventura,E S, AU - Rostami,A, PY - 1999/3/30/pubmed PY - 1999/3/30/medline PY - 1999/3/30/entrez SP - 2 EP - 9 JF - Multiple sclerosis (Houndmills, Basingstoke, England) JO - Mult. Scler. VL - 5 IS - 1 N2 - Immunological tolerance and suppression of clinical and histological experimental allergic encaphalomyelitis (EAE) can be induced by the intravenous (i.v.) administration of myelin basic protein (MBP). In this report we have characterized the effect of the time of i.v. administration of MBP on the course of EAE in Lewis rats. Rats were treated with the i.v. administration of one or two 500 micrograms doses of MBP either before or after active immunization. Results indicated that i.v. administration of MBP in rats before active immunization with MBP/CFA (naïve rats) was most effective when given 14 days before active immunization, but treatment of rats actively immunized with MBP (immunized rats) was most effective at the onset of disease. Treatment at other times was less effective. The i.v. administration of the peptide MBP 68-88 (p68-88) containing the dominant encephalitogenic epitope could also suppress MBP-induced EAE in a dose dependent manner. Intravenous administration of two injections of p68-88 to naïve rats on days 10 and 3 before, or on days 0 and 7 after, active immunization with MBP suppressed the development of EAE in a dose dependent manner. Treatment of rats with i.v. MBP after, but not before, the transfer of MBP-reactive EAE effector cells suppressed the development of EAE in the recipient rats. Transfer of lymphoid cells from tolerized naïve rats failed to protect recipient rats against development of active or passive EAE. These results indicate the importance of timing and dose of the antigen on the induction of tolerance and suggests different mechanisms of tolerance induction by intravenous MBP in immunized and naïve rats. They also emphasize the importance of timing in designing efficient treatment strategies when i.v. tolerance is contemplated in EAE and possibly multiple sclerosis. SN - 1352-4585 UR - https://www.unboundmedicine.com/medline/citation/10096096/Effect_of_timing_of_intravenous_administration_of_myelin_basic_protein_on_the_induction_of_tolerance_in_experimental_allergic_encephalomyelitis_ L2 - http://journals.sagepub.com/doi/full/10.1191/135245899701564308?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -