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PMID: 1370356 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 1 ·1992-01-01 ·Pages 421-5

Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL

Abstract

Oral administration of myelin basic protein (MBP) is an effective way of suppressing experimental autoimmune encephalomyelitis (EAE). We have previously shown that such suppression is mediated by CD8+ T cells, which adoptively transfer protection and suppress immune responses in vitro. In the present study we have found that modulator cells from animals orally tolerized to MBP produce a suppressor factor upon stimulation with MBP in vitro that is specifically inhibited by anti-transforming growth factor beta (TGF-beta) neutralizing antibodies. No effect was observed with antibodies to gamma interferon, tumor necrosis factor alpha/beta, or indomethacin. In addition, the active form of the type 1 isoform of TGF-beta 1 (TGF-beta 1) can be directly demonstrated in the supernatants of cells from animals orally tolerized to MBP or ovalbumin after antigen stimulation in vitro. Antiserum specific for TGF-beta 1 administered in vivo abrogated the protective effect of oral tolerization to MBP in EAE. Furthermore, injection of anti-TGF-beta 1 serum to nontolerized EAE animals resulted in an increase in severity and duration of disease. These results suggest that immunomodulation of EAE induced by oral tolerization to MBP and natural recovery mechanisms use a common immunoregulatory pathway that is dependent on TGF-beta 1. Implications of such an association are of therapeutic relevance to human autoimmune diseases and may help to explain one of the mechanisms involved in the mediation of active suppression by T cells.

MeSH Terms
Administration, Oral Animals CD8 Antigens/analysis Encephalomyelitis, Autoimmune, Experimental/immunology Hypersensitivity, Delayed/immunology Immune Tolerance Lymphocyte Activation Myelin Basic Protein/administration & dosage,immunology Rats Rats, Inbred Lew T-Lymphocyte Subsets/immunology T-Lymphocytes, Regulatory/immunology Transforming Growth Factor beta/physiology
Chemicals
CD8 Antigens Myelin Basic Protein Transforming Growth Factor beta
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Miller A
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Lider O
Roberts A B
Sporn M B
Weiner H L
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46 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.1.421
Published
1992-01-01
Pages
421-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48249
Subset
IM
Grants
FIC NIH HHS · 1F05TW04418, 1CP · United States
PHS HHS · N529352 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.1.421 PMC Full Text View journal details
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