Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II
In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T ce...
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| Veröffentlicht in: | The Journal of experimental medicine 2004-05, Vol.199 (9), p.1285-1291 |
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| creator | Kriegel, Martin A Lohmann, Tobias Gabler, Christoph Blank, Norbert Kalden, Joachim R Lorenz, Hanns-Martin |
| description | In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T cells (T(regs)) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. T(regs) from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II T(regs) were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general. |
| doi_str_mv | 10.1084/jem.20032158 |
| format | Article |
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Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T cells (T(regs)) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. T(regs) from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II T(regs) were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20032158</identifier><identifier>PMID: 15117972</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Addison Disease - immunology ; Adult ; Aged ; Antigens, CD - immunology ; Autoimmune Diseases - immunology ; Brief Definitive Report ; CD4-Positive T-Lymphocytes - immunology ; Diabetes Mellitus, Type 1 - immunology ; Female ; Humans ; Male ; Middle Aged ; Polyendocrinopathies, Autoimmune - immunology ; Receptors, Interleukin-2 - immunology ; T-Lymphocytes - immunology ; Thyroiditis, Autoimmune - immunology</subject><ispartof>The Journal of experimental medicine, 2004-05, Vol.199 (9), p.1285-1291</ispartof><rights>Copyright © 2004, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-5e196ada8de81066de86212fb7e1a8ba4c0e95b3d805f5c8cd69b5789bc645633</citedby><cites>FETCH-LOGICAL-c380t-5e196ada8de81066de86212fb7e1a8ba4c0e95b3d805f5c8cd69b5789bc645633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15117972$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kriegel, Martin A</creatorcontrib><creatorcontrib>Lohmann, Tobias</creatorcontrib><creatorcontrib>Gabler, Christoph</creatorcontrib><creatorcontrib>Blank, Norbert</creatorcontrib><creatorcontrib>Kalden, Joachim R</creatorcontrib><creatorcontrib>Lorenz, Hanns-Martin</creatorcontrib><title>Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T cells (T(regs)) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. T(regs) from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II T(regs) were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. 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Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T cells (T(regs)) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. T(regs) from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II T(regs) were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. 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| subjects | Addison Disease - immunology Adult Aged Antigens, CD - immunology Autoimmune Diseases - immunology Brief Definitive Report CD4-Positive T-Lymphocytes - immunology Diabetes Mellitus, Type 1 - immunology Female Humans Male Middle Aged Polyendocrinopathies, Autoimmune - immunology Receptors, Interleukin-2 - immunology T-Lymphocytes - immunology Thyroiditis, Autoimmune - immunology |
| title | Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II |
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