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- Title
CD4<sup>+</sup>CD25<sup>+</sup> Regulatory T-Cells Inhibit the Islet Innate Immune Response and Promote Islet Engraftment.
- Authors
Chen, Dongmei; Zhang, Nan; Fu, Shuang; Schröppel, Bernd; Guo, Qiongfen; Garin, Alexandre; Lira, Sergio A.; Bromberg, Jonathan S.
- Abstract
Early islet cell loss is a significant problem in clinical islet cell transplantation. Diverse stress stimuli induce innate immune responses in islets that contribute to β-cell dysfunction, inflammation, and loss. Here, we show that cytokine-stimulated murine islets express multiple inflammatory chemokines that recruit T-cells and thereby impair islet function in vitro and in vivo. Both nonislet ductal and exocrine elements and the individual islet cellular components contribute to this innate immune response. CD4+CD25+ regulatory T-cells inhibit islet chemokine expression through a cell contact-dependent, soluble factor-independent mechanism and inhibit effector T-cell migration to the islet. Regulatory T-cells can also migrate to stimulated islets. Cotransfer of regulatory T-cells with islets in a transplantation model prevents islet innate immune responses and inflammation and preserves normal architecture and engraftment. Regulatory T-cell inhibition of multiple components of innate immune responses may be a fundamental aspect of their function that influences ischemia-reperfusion injury and adaptive immunity. Diabetes 55:1011-1021, 2006
- Subjects
ISLANDS of Langerhans; CELL transplantation; PHYSIOLOGICAL stress; IMMUNE response; INFLAMMATION
- Publication
Diabetes, 2006, Vol 55, Issue 4, p1011
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.55.04.06.db05-1048