rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1996-2-22
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pubmed:abstractText |
Orally administered antigens induce a state of immunologic hyporesponsiveness termed oral tolerance. Different mechanisms are involved in mediating oral tolerance depending on the dose fed. Low doses of antigen generate cytokine-secreting regulatory cells, whereas high doses induce anergy or deletion. We used mice transgenic for a T-cell receptor (TCR) derived from an encephalitogenic T-cell clone specific for the acetylated N-terminal peptide of myelin basic protein (MBP) Ac-1-11 plus I-Au to test whether a regulatory T cell could be generated from the same precursor cell as that of an encephalitogenic Th1 cell and whether the induction was dose dependent. The MBP TCR transgenic mice primarily have T cells of a precursor phenotype that produce interleukin 2 (IL-2) with little interferon gamma (IFN-gamma), IL-4, or transforming growth factor beta (TGF-beta). We fed transgenic animals a low-dose (1 mg x 5) or high-dose (25 mg x 1) regimen of mouse MBP and without further immunization spleen cells were tested for cytokine production. Low-dose feeding induced prominent secretion of IL-4, IL-10, and TGF-beta, whereas minimal secretion of these cytokines was observed with high-dose feeding. Little or no change was seen in proliferation or IL-2/IFN-gamma secretion in fed animals irrespective of the dose. To demonstrate in vivo functional activity of the cytokine-secreting cells generated by oral antigen, spleen cells from low-dose-fed animals were adoptively transferred into naive (PLJ x SJL)F1 mice that were then immunized for the development of experimental autoimmune encephalomyelitis (EAE). Marked suppression of EAE was observed when T cells were transferred from MBP-fed transgenic animals but not from animals that were not fed. In contrast to oral tolerization, s.c. immunization of transgenic animals with MBP in complete Freund's adjuvant induced IFN-gamma-secreting Th1 cells in vitro and experimental encephalomyelitis in vivo. Despite the large number of cells reactive to MBP in the transgenic animals, EAE was also suppressed by low-dose feeding of MBP prior to immunization. These results demonstrate that MBP-specific T cells can differentiate in vivo into encephalitogenic or regulatory T cells depending upon the context by which they are exposed to antigen.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-1370356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-1548698,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-2025413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-2190093,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-2474183,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-2611224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-3709525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-6251047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-6667333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-6972088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7520367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7520605,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7530361,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7603570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7664081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7678116,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7693817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7744081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7877175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-7925432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-8011298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-8022835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-8255292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-8262237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-8352587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-8369276,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552644-8381670
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
93
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
388-91
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8552644-Administration, Oral,
pubmed-meshheading:8552644-Animals,
pubmed-meshheading:8552644-Dose-Response Relationship, Immunologic,
pubmed-meshheading:8552644-Encephalomyelitis, Autoimmune, Experimental,
pubmed-meshheading:8552644-Immune Tolerance,
pubmed-meshheading:8552644-Interferon-gamma,
pubmed-meshheading:8552644-Interleukin-10,
pubmed-meshheading:8552644-Interleukin-2,
pubmed-meshheading:8552644-Interleukin-4,
pubmed-meshheading:8552644-Lymphocyte Activation,
pubmed-meshheading:8552644-Mice,
pubmed-meshheading:8552644-Mice, Inbred C57BL,
pubmed-meshheading:8552644-Mice, Transgenic,
pubmed-meshheading:8552644-Myelin Basic Proteins,
pubmed-meshheading:8552644-Receptors, Antigen, T-Cell,
pubmed-meshheading:8552644-Transforming Growth Factor beta
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pubmed:year |
1996
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pubmed:articleTitle |
Oral tolerance in myelin basic protein T-cell receptor transgenic mice: suppression of autoimmune encephalomyelitis and dose-dependent induction of regulatory cells.
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pubmed:affiliation |
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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