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pubmed-2119389
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| recordtype |
oai_dc
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| spelling |
pubmed-21193892008-04-16 Induction of tolerance to autoimmune diabetes with islet antigens Articles The development of T cell tolerance to self-antigens is imparted principally through negative selection events during thymic ontogeny. However, this tolerance may be limited to antigens that are expressed in the thymus, and additional mechanisms are probably required to regulate autoimmune responses to tissue-specific antigens. Autoimmune diabetes can be induced experimentally by treating susceptible stains of mice with multiple low doses of streptozotocin (STZ). In this report we show that transplantation of isolated islets of Langerhans into the thymuses of adult C57BL/KsJ mice will induce tolerance to the subsequent induction of autoimmune diabetes. This tolerance is tissue specific and thymus dependent. It was not induced by thymic transfer of adrenal tissue or by kidney transfer of islets. Furthermore, depletion of mature T cells was required and the tolerant state was abrogated by the adoptive transfer of normal splenocytes. It is interesting that pretreatment of the islets with STZ enhanced their ability to induce tolerance, and suggests that antigen shedding induced by tissue damage may facilitate transfer of islet antigens to tolerizing cells in the thymus. These findings indicate that thymic tolerance specific for tissue can be stimulated to occur in the presence of atopic tissue- specific intrathymic antigens. Elimination of disease-related T cells in the absence of global immunosuppression represents a novel approach for the prevention of autoimmune disease. The Rockefeller University Press 1992-10-01 /pmc/articles/PMC2119389/ /pubmed/1402656 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
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| repository_type |
Open Access Journal
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| institution_category |
Foreign Institution
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| institution |
US National Center for Biotechnology Information
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| building |
NCBI PubMed
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| collection |
Online Access
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| language |
English
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| format |
Online
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| title |
Induction of tolerance to autoimmune diabetes with islet antigens
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| spellingShingle |
Induction of tolerance to autoimmune diabetes with islet antigens
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| title_short |
Induction of tolerance to autoimmune diabetes with islet antigens
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| title_full |
Induction of tolerance to autoimmune diabetes with islet antigens
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| title_fullStr |
Induction of tolerance to autoimmune diabetes with islet antigens
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| title_full_unstemmed |
Induction of tolerance to autoimmune diabetes with islet antigens
|
| title_sort |
induction of tolerance to autoimmune diabetes with islet antigens
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| description |
The development of T cell tolerance to self-antigens is imparted principally through negative selection events during thymic ontogeny. However, this tolerance may be limited to antigens that are expressed in the thymus, and additional mechanisms are probably required to regulate autoimmune responses to tissue-specific antigens. Autoimmune diabetes can be induced experimentally by treating susceptible stains of mice with multiple low doses of streptozotocin (STZ). In this report we show that transplantation of isolated islets of Langerhans into the thymuses of adult C57BL/KsJ mice will induce tolerance to the subsequent induction of autoimmune diabetes. This tolerance is tissue specific and thymus dependent. It was not induced by thymic transfer of adrenal tissue or by kidney transfer of islets. Furthermore, depletion of mature T cells was required and the tolerant state was abrogated by the adoptive transfer of normal splenocytes. It is interesting that pretreatment of the islets with STZ enhanced their ability to induce tolerance, and suggests that antigen shedding induced by tissue damage may facilitate transfer of islet antigens to tolerizing cells in the thymus. These findings indicate that thymic tolerance specific for tissue can be stimulated to occur in the presence of atopic tissue- specific intrathymic antigens. Elimination of disease-related T cells in the absence of global immunosuppression represents a novel approach for the prevention of autoimmune disease.
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| publisher |
The Rockefeller University Press
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| publishDate |
1992
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| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119389/
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| _version_ |
1611415321879511040
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