Aspirin modified dendritic cells are potent inducers of allo-specific regulatory T-cells

被引:38
作者
Buckland, Matthew [1 ]
Jago, Charlotte
Fazekesova, Henrieta
George, Andrew
Lechler, Robert
Lombardi, Giovanna
机构
[1] Kings Coll Hosp London, Sch Med Guys, Dept Nephrol & Transplantat, Immunoregulat Labs, London SE1 9RT, England
[2] St Thomas Hosp, London SE1 9RT, England
[3] Univ London Imperial Coll Sci Technol & Med, Dept Immunol, London W12 0NN, England
基金
英国医学研究理事会;
关键词
aspirin; dendritic cells; regulatory T-cells;
D O I
10.1016/j.intimp.2006.07.008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 [免疫学];
摘要
Salicylic acid (aspirin) is a widely used pharmacological agent with immunodmodulatory properties. Dendritic cells are key regulators of the immune response, and are capable of inducing hyporesponsiveness and regulatory activity in CD4(+) T-cells. We have demonstrated that aspirin-treated dendritic cells are effective at antigen processing and presentation, and possess a unique potency for inducing regulatory activity in responder T-cells. Unlike immature dendritic cells, aspirin DCs are resistant to the effects of maturational stimuli, as determined by low levels of CD40, CD80, CD83 and CD86 expression. Aspirin DCs were demonstrated to express high levels of the co-inhibitor of T-cell activation ILT-3. Aspirin DCs themselves produce less IL-10 and more IL-12 than immature DCs, but no specific cytokine is necessary for their tolerogenic capacity. When naive CD4(+) T-cells are exposed to aspirin DCs they produce significant levels of IFN gamma but these same T-cells are hypo-proliferative. Aspirin-treated DCs demonstrate the characteristics of a potential immunotherapy for controlling unwanted immune-responses Such as the indirect pathway of allo-recognition that drives chronic allograft rejection. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:1895 / 1901
页数:7
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