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Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals.
Eur J Immunol 1994; 24(5):1026-32EJ

Abstract

Antigen-driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co-culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6-8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases.

Authors+Show Affiliations

Department of Neurology, Carmel Medical Center, Haifa, Israel.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7514126

Citation

Miller, A, et al. "Orally Administered Myelin Basic Protein in Neonates Primes for Immune Responses and Enhances Experimental Autoimmune Encephalomyelitis in Adult Animals." European Journal of Immunology, vol. 24, no. 5, 1994, pp. 1026-32.
Miller A, Lider O, Abramsky O, et al. Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals. Eur J Immunol. 1994;24(5):1026-32.
Miller, A., Lider, O., Abramsky, O., & Weiner, H. L. (1994). Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals. European Journal of Immunology, 24(5), pp. 1026-32.
Miller A, et al. Orally Administered Myelin Basic Protein in Neonates Primes for Immune Responses and Enhances Experimental Autoimmune Encephalomyelitis in Adult Animals. Eur J Immunol. 1994;24(5):1026-32. PubMed PMID: 7514126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals. AU - Miller,A, AU - Lider,O, AU - Abramsky,O, AU - Weiner,H L, PY - 1994/5/1/pubmed PY - 1994/5/1/medline PY - 1994/5/1/entrez SP - 1026 EP - 32 JF - European journal of immunology JO - Eur. J. Immunol. VL - 24 IS - 5 N2 - Antigen-driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co-culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6-8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/7514126/Orally_administered_myelin_basic_protein_in_neonates_primes_for_immune_responses_and_enhances_experimental_autoimmune_encephalomyelitis_in_adult_animals_ L2 - https://doi.org/10.1002/eji.1830240503 DB - PRIME DP - Unbound Medicine ER -