期刊
HEPATOLOGY
卷 50, 期 2, 页码 612-621出版社
WILEY
DOI: 10.1002/hep.23043
关键词
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK47757]
- National Heart, Lung and Blood Institute [P01 HL59407]
- National Institute of Child Health and Human Development [P01 HD57247]
- Glaxo SmithKline, Inc.
The mechanisms of tolerance in the liver that limit susceptibility to food allergy and that mediate the acceptance of liver transplants, even with a complete major histocompatibility complex (MHC) mismatch, remain poorly defined. Here we report that in a model of liver-directed gene transfer, cytotoxic T lymphocyte (CTL) responses to non-self antigens are controlled by hepatic regulatory T cells (Tregs) that secrete the immunosuppressive cytokine interleukin (IL)-10 in response to the antigen. In addition, Kupffer cells (KCs), normally thought to initiate immune responses, are rendered tolerogenic in this context. The depletion of KCs results in a complete abrogation of IL-10 production by hepatic Tregs, indicating an interaction between Tregs and KCs in the induction of tolerance. Conclusion: Our study suggests that hepatic Tregs together with KCs create a local suppressive microenvironment that prevents the establishment of the CTL response. These mechanisms provide pivotal insights and may prove instrumental in the tolerization toward non-self therapeutic proteins delivered to the liver. (HEPATOLOGY 2009;50:612-621.)
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