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Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. VI. Suppression of adoptively transferred disease and differential effects of oral vs. intravenous tolerization.
J Neuroimmunol 1993; 46(1-2):73-82JN

Abstract

Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously shown that oral administration of myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis (EAE) when it is actively induced by MBP emulsified in complete Freund's adjuvant. In order to further study antigen-driven tolerance in this model, we investigated the effect of oral tolerization on adoptively transferred EAE and compared oral tolerance to intravenously (i.v.) administered MBP in both actively induced EAE and adoptively transferred EAE. Although orally tolerized animals were not protected from adoptively transferred EAE, spleen cells from orally tolerized animals suppressed adoptively transferred EAE when co-transferred with encephalitogenic cells or when injected into recipient animals at a different site at the time encephalitogenic cells were transferred. This suppression was mediated by CD8+ T cells, correlated with suppression of DTH responses to MBP, and was associated with decreased inflammation in the spinal cord. Unlike oral tolerization, spleen cells from i.v. tolerized animals did not suppress adoptively transferred EAE when co-transferred with encephalitogenic cells although i.v. tolerized animals were protected from adoptively transferred EAE. MBP peptides were then utilized to further characterize differences between i.v. and oral tolerization in the actively induced disease model. Both orally and intravenously administered MBP suppressed actively induced EAE. However, EAE was only suppressed by prior i.v. tolerization with the encephalitogenic MBP peptide 71-90, but not with the non-encephalitogenic peptide 21-40, whereas prior tolerization with 21-40 did suppress actively induced EAE when administered orally. These results suggest a different mechanism of tolerance is initiated by oral vs. intravenous administered antigen. Specifically, oral tolerization suppresses primarily by the generation of active suppression whereas the dominant mechanism of suppression associated with i.v. tolerization appears most consistent with the elicitation of clonal anergy.

Authors+Show Affiliations

Department of Medicine, Brigham and Women's Hospital, Boston, MA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7689596

Citation

Miller, A, et al. "Suppression of Experimental Autoimmune Encephalomyelitis By Oral Administration of Myelin Basic Protein. VI. Suppression of Adoptively Transferred Disease and Differential Effects of Oral Vs. Intravenous Tolerization." Journal of Neuroimmunology, vol. 46, no. 1-2, 1993, pp. 73-82.
Miller A, Zhang ZJ, Sobel RA, et al. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. VI. Suppression of adoptively transferred disease and differential effects of oral vs. intravenous tolerization. J Neuroimmunol. 1993;46(1-2):73-82.
Miller, A., Zhang, Z. J., Sobel, R. A., al-Sabbagh, A., & Weiner, H. L. (1993). Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. VI. Suppression of adoptively transferred disease and differential effects of oral vs. intravenous tolerization. Journal of Neuroimmunology, 46(1-2), pp. 73-82.
Miller A, et al. Suppression of Experimental Autoimmune Encephalomyelitis By Oral Administration of Myelin Basic Protein. VI. Suppression of Adoptively Transferred Disease and Differential Effects of Oral Vs. Intravenous Tolerization. J Neuroimmunol. 1993;46(1-2):73-82. PubMed PMID: 7689596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. VI. Suppression of adoptively transferred disease and differential effects of oral vs. intravenous tolerization. AU - Miller,A, AU - Zhang,Z J, AU - Sobel,R A, AU - al-Sabbagh,A, AU - Weiner,H L, PY - 1993/7/1/pubmed PY - 2000/6/1/medline PY - 1993/7/1/entrez SP - 73 EP - 82 JF - Journal of neuroimmunology JO - J. Neuroimmunol. VL - 46 IS - 1-2 N2 - Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously shown that oral administration of myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis (EAE) when it is actively induced by MBP emulsified in complete Freund's adjuvant. In order to further study antigen-driven tolerance in this model, we investigated the effect of oral tolerization on adoptively transferred EAE and compared oral tolerance to intravenously (i.v.) administered MBP in both actively induced EAE and adoptively transferred EAE. Although orally tolerized animals were not protected from adoptively transferred EAE, spleen cells from orally tolerized animals suppressed adoptively transferred EAE when co-transferred with encephalitogenic cells or when injected into recipient animals at a different site at the time encephalitogenic cells were transferred. This suppression was mediated by CD8+ T cells, correlated with suppression of DTH responses to MBP, and was associated with decreased inflammation in the spinal cord. Unlike oral tolerization, spleen cells from i.v. tolerized animals did not suppress adoptively transferred EAE when co-transferred with encephalitogenic cells although i.v. tolerized animals were protected from adoptively transferred EAE. MBP peptides were then utilized to further characterize differences between i.v. and oral tolerization in the actively induced disease model. Both orally and intravenously administered MBP suppressed actively induced EAE. However, EAE was only suppressed by prior i.v. tolerization with the encephalitogenic MBP peptide 71-90, but not with the non-encephalitogenic peptide 21-40, whereas prior tolerization with 21-40 did suppress actively induced EAE when administered orally. These results suggest a different mechanism of tolerance is initiated by oral vs. intravenous administered antigen. Specifically, oral tolerization suppresses primarily by the generation of active suppression whereas the dominant mechanism of suppression associated with i.v. tolerization appears most consistent with the elicitation of clonal anergy. SN - 0165-5728 UR - https://www.unboundmedicine.com/medline/citation/7689596/Suppression_of_experimental_autoimmune_encephalomyelitis_by_oral_administration_of_myelin_basic_protein__VI__Suppression_of_adoptively_transferred_disease_and_differential_effects_of_oral_vs__intravenous_tolerization_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0165-5728(93)90235-Q DB - PRIME DP - Unbound Medicine ER -