Tags

Type your tag names separated by a space and hit enter

Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy.
J Immunol. 1991 Oct 01; 147(7):2155-63.JI

Abstract

We have recently reported that experimental autoimmune encephalomyelitis (EAE) can be suppressed by the oral administration of myelin basic protein (MBP). The oral introduction of 20 mg MBP together with a trypsin inhibitor results in inhibition of EAE clinical signs, decreased CNS histopathologic changes and dramatically reduced MBP-specific proliferative responses in fed and challenged Lewis rats. In the present study, we have investigated the mechanism underlying MBP-induced oral tolerance in EAE. Neither lymphoid cells (lymph node cells, spleen cells, Peyer's patch lymphocytes, thymocytes) nor humoral elements derived from tolerant donors were capable of transferring the tolerance to naive recipients. Moreover, lymphoid cells obtained from orally tolerant donors exhibited a marked decrease in their capacity to transfer EAE to naive recipient rats, even after in vitro activation with MBP or Con A. We observed that EAE could be readily transferred into orally tolerant rats using MBP-specific encephalitogenic T cell lines. In vitro cell mixing studies showed that the proliferation of lymphocytes from MBP-sensitized donors was not inhibited by the addition of lymphoid cells from tolerant donors, arguing against the role of a suppressor cell. Investigation of MBP-stimulated lymphokine production showed that both IL-2 and IFN-gamma levels were substantially decreased in spleen and lymph node cell cultures from MBP-fed rats compared to vehicle-fed control animals. Furthermore, limiting dilution analyses revealed that MBP-fed rats exhibited a profound decrease in MBP-reactive, IL-2-secreting lymphocytes relative to control animals. Thus, because lymphocytes from MBP-fed rats neither proliferate nor secrete IL-2 or IFN-gamma in response to MBP and we can find no compelling evidence for the role of suppressor cells, we propose that the oral administration of MBP results in a state of clonal anergy.

Authors+Show Affiliations

Department of Medical Microbiology and Immunology, Ohio State University College of Medicine, Columbus 43210.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

1717550

Citation

Whitacre, C C., et al. "Oral Tolerance in Experimental Autoimmune Encephalomyelitis. III. Evidence for Clonal Anergy." Journal of Immunology (Baltimore, Md. : 1950), vol. 147, no. 7, 1991, pp. 2155-63.
Whitacre CC, Gienapp IE, Orosz CG, et al. Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy. J Immunol. 1991;147(7):2155-63.
Whitacre, C. C., Gienapp, I. E., Orosz, C. G., & Bitar, D. M. (1991). Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy. Journal of Immunology (Baltimore, Md. : 1950), 147(7), 2155-63.
Whitacre CC, et al. Oral Tolerance in Experimental Autoimmune Encephalomyelitis. III. Evidence for Clonal Anergy. J Immunol. 1991 Oct 1;147(7):2155-63. PubMed PMID: 1717550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy. AU - Whitacre,C C, AU - Gienapp,I E, AU - Orosz,C G, AU - Bitar,D M, PY - 1991/10/1/pubmed PY - 1991/10/1/medline PY - 1991/10/1/entrez SP - 2155 EP - 63 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 147 IS - 7 N2 - We have recently reported that experimental autoimmune encephalomyelitis (EAE) can be suppressed by the oral administration of myelin basic protein (MBP). The oral introduction of 20 mg MBP together with a trypsin inhibitor results in inhibition of EAE clinical signs, decreased CNS histopathologic changes and dramatically reduced MBP-specific proliferative responses in fed and challenged Lewis rats. In the present study, we have investigated the mechanism underlying MBP-induced oral tolerance in EAE. Neither lymphoid cells (lymph node cells, spleen cells, Peyer's patch lymphocytes, thymocytes) nor humoral elements derived from tolerant donors were capable of transferring the tolerance to naive recipients. Moreover, lymphoid cells obtained from orally tolerant donors exhibited a marked decrease in their capacity to transfer EAE to naive recipient rats, even after in vitro activation with MBP or Con A. We observed that EAE could be readily transferred into orally tolerant rats using MBP-specific encephalitogenic T cell lines. In vitro cell mixing studies showed that the proliferation of lymphocytes from MBP-sensitized donors was not inhibited by the addition of lymphoid cells from tolerant donors, arguing against the role of a suppressor cell. Investigation of MBP-stimulated lymphokine production showed that both IL-2 and IFN-gamma levels were substantially decreased in spleen and lymph node cell cultures from MBP-fed rats compared to vehicle-fed control animals. Furthermore, limiting dilution analyses revealed that MBP-fed rats exhibited a profound decrease in MBP-reactive, IL-2-secreting lymphocytes relative to control animals. Thus, because lymphocytes from MBP-fed rats neither proliferate nor secrete IL-2 or IFN-gamma in response to MBP and we can find no compelling evidence for the role of suppressor cells, we propose that the oral administration of MBP results in a state of clonal anergy. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1717550/Oral_tolerance_in_experimental_autoimmune_encephalomyelitis__III__Evidence_for_clonal_anergy_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=1717550 DB - PRIME DP - Unbound Medicine ER -