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Oral administration of myelin induces antigen-specific TGF-beta 1 secreting T cells in patients with multiple sclerosis.
Ann N Y Acad Sci. 1997 Dec 19; 835:120-31.AN

Abstract

Oral administration of antigen is a long-recognized method of inducing systemic immune tolerance. In animals with experimental autoimmune disease, a major mechanism of oral tolerance involves the induction of regulatory T cells that mediate active suppression by secreting the cytokine TGF-beta 1. Multiple sclerosis (MS) is a presumed T cell-mediated Th1 type autoimmune disease. In this paper we investigated, in patients with MS, whether oral myelin treatment (myelin containing both MBP and PLP) induced antigen-specific MBP- or PLP-reactive T cells that were either Th2-like (secreted IL-4 or TGF-beta 1), or alternatively whether Th1 type sensitization occurred as measured by IFN-gamma secretion. Specifically, 4,860 short-term T cell lines were generated to either MBP, PLP or TT from 34 relapsing-remitting patients with MS; 17 were orally treated with bovine myelin daily for a minimum of two years as compared to 17 non-treated patients. We found a marked increase in the relative frequencies of both MBP- and PLP-specific TGF-beta 1 secreting T cell lines in the myelin-treated MS patients as compared to non-treated MS patients (MBP, p < 0.001; PLP, p < 0.003). In contrast, no changes in the frequency of MBP- or PLP-specific IFN-gamma or TT-specific TGF-beta 1 secreting T cells were observed. These results suggest that the oral administration of antigens generates antigen-specific TGF-beta 1 secreting T cells of presumed mucosal origin that may represent a distinct cytokine-secreting lineage of T cells (Th3). Since, in animal models, antigen-specific TGF-beta 1 secreting cells localize to the target organ and then suppress inflammation in the local microenvironment, oral tolerization with self-antigens may provide a therapeutic approach for the treatment of cell-mediated autoimmune disease which does not depend upon knowledge of the antigen specificity of the original T cell clone triggering the autoimmune cascade.

Authors+Show Affiliations

Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. hafler@CND.BWH.Harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9616767

Citation

Hafler, D A., et al. "Oral Administration of Myelin Induces Antigen-specific TGF-beta 1 Secreting T Cells in Patients With Multiple Sclerosis." Annals of the New York Academy of Sciences, vol. 835, 1997, pp. 120-31.
Hafler DA, Kent SC, Pietrusewicz MJ, et al. Oral administration of myelin induces antigen-specific TGF-beta 1 secreting T cells in patients with multiple sclerosis. Ann N Y Acad Sci. 1997;835:120-31.
Hafler, D. A., Kent, S. C., Pietrusewicz, M. J., Khoury, S. J., Weiner, H. L., & Fukaura, H. (1997). Oral administration of myelin induces antigen-specific TGF-beta 1 secreting T cells in patients with multiple sclerosis. Annals of the New York Academy of Sciences, 835, 120-31.
Hafler DA, et al. Oral Administration of Myelin Induces Antigen-specific TGF-beta 1 Secreting T Cells in Patients With Multiple Sclerosis. Ann N Y Acad Sci. 1997 Dec 19;835:120-31. PubMed PMID: 9616767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral administration of myelin induces antigen-specific TGF-beta 1 secreting T cells in patients with multiple sclerosis. AU - Hafler,D A, AU - Kent,S C, AU - Pietrusewicz,M J, AU - Khoury,S J, AU - Weiner,H L, AU - Fukaura,H, PY - 1998/6/9/pubmed PY - 1998/6/9/medline PY - 1998/6/9/entrez SP - 120 EP - 31 JF - Annals of the New York Academy of Sciences JO - Ann. N. Y. Acad. Sci. VL - 835 N2 - Oral administration of antigen is a long-recognized method of inducing systemic immune tolerance. In animals with experimental autoimmune disease, a major mechanism of oral tolerance involves the induction of regulatory T cells that mediate active suppression by secreting the cytokine TGF-beta 1. Multiple sclerosis (MS) is a presumed T cell-mediated Th1 type autoimmune disease. In this paper we investigated, in patients with MS, whether oral myelin treatment (myelin containing both MBP and PLP) induced antigen-specific MBP- or PLP-reactive T cells that were either Th2-like (secreted IL-4 or TGF-beta 1), or alternatively whether Th1 type sensitization occurred as measured by IFN-gamma secretion. Specifically, 4,860 short-term T cell lines were generated to either MBP, PLP or TT from 34 relapsing-remitting patients with MS; 17 were orally treated with bovine myelin daily for a minimum of two years as compared to 17 non-treated patients. We found a marked increase in the relative frequencies of both MBP- and PLP-specific TGF-beta 1 secreting T cell lines in the myelin-treated MS patients as compared to non-treated MS patients (MBP, p < 0.001; PLP, p < 0.003). In contrast, no changes in the frequency of MBP- or PLP-specific IFN-gamma or TT-specific TGF-beta 1 secreting T cells were observed. These results suggest that the oral administration of antigens generates antigen-specific TGF-beta 1 secreting T cells of presumed mucosal origin that may represent a distinct cytokine-secreting lineage of T cells (Th3). Since, in animal models, antigen-specific TGF-beta 1 secreting cells localize to the target organ and then suppress inflammation in the local microenvironment, oral tolerization with self-antigens may provide a therapeutic approach for the treatment of cell-mediated autoimmune disease which does not depend upon knowledge of the antigen specificity of the original T cell clone triggering the autoimmune cascade. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/9616767/Oral_administration_of_myelin_induces_antigen_specific_TGF_beta_1_secreting_T_cells_in_patients_with_multiple_sclerosis_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0077-8923&amp;date=1997&amp;volume=835&amp;spage=120 DB - PRIME DP - Unbound Medicine ER -