| Early Treatment of NOD Mice With B7-H4 Reduces the Incidence of Autoimmune Diabetes. | |
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MedLine Citation:
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PMID: 21984581 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVEAutoimmune diabetes is a T cell-mediated disease in which insulin-producing β-cells are destroyed. Autoreactive T cells play a central role in mediating β-cell destruction. B7-H4 is a negative cosignaling molecule that downregulates T-cell responses. In this study, we aim to determine the role of B7-H4 on regulation of β-cell-specific autoimmune responses.RESEARCH DESIGN AND METHODSPrediabetic (aged 3 weeks) female NOD mice (group 1, n = 21) were treated with intraperitoneal injections of B7-H4.Ig at 7.5 mg/kg, with the same amount of mouse IgG (group 2, n = 24), or with no protein injections (group 3, n = 24), every 3 days for 12 weeks.RESULTSB7-H4.Ig reduced the incidence of autoimmune diabetes, compared with the control groups (diabetic mice 28.6% of group 1, 66.7% of group 2 [P = 0.0081], and 70.8% of group 3 [group 1 vs. 3, P = 0.0035]). Histological analysis revealed that B7-H4 treatment did not block islet infiltration but rather suppressed further infiltrates after 9 weeks of treatment (group 1 vs. 2, P = 0.0003). B7-H4 treatment also reduced T-cell proliferation in response to GAD65 stimulation ex vivo. The reduction of diabetes is not due to inhibition of activated T cells in the periphery but rather to a transient increase of Foxp3(+) CD4(+) T-cell population at one week posttreatment (12.88 ± 1.29 vs. 11.58 ± 1.46%; n = 8; P = 0.03).CONCLUSIONSOur data demonstrate the protective role of B7-H4 in the development of autoimmune diabetes, suggesting a potential means of preventing type 1 diabetes by targeting the B7-H4 pathway. |
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Authors:
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Xiaojie Wang; Jianqiang Hao; Daniel L Metzger; Alice Mui; Ziliang Ao; Noushin Akhoundsadegh; Solomon Langermann; Linda Liu; Lieping Chen; Dawei Ou; C Bruce Verchere; Garth L Warnock |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-7 |
Journal Detail:
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Title: Diabetes Volume: - ISSN: 1939-327X ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; the. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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