IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection: Paradoxical post-transplantation effects of IFN-γ

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• 作者：Xiaoguang Xu ; PhD¹ ; Haiyan Huang ; PhD¹ ; Qiang Wang ; MD¹ ; Ming Cai ; Yeyong Qian ; MD ; Yong Han ; MD ; Xinying Wang ; MD ; Yu Gao ; Ming Yuan ; MD ; Liang Xu ; MD ; Chen Yao ; PhD ; Li Xiao ; PhD ; ^{xiaolilab309@163.com} ; Bingyi Shi ; MD ; ^{shibingyi@medmail.com.cn}
• 关键词：Kidney transplantation ; Acute cellular renal allograft rejection ; Interferon-γ ; Regulatory t cell
• 刊名：Immunobiology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：222
• 期：2
• 页码：280-290
• 全文大小：3259 K
• 卷排序：222

文摘

IFN-γ is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-γ can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-γ secreted by Th1-like regulatory T cells in human kidney transplantation.MethodsTo determine the function of IFN-γ in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACR patients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-γ in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively.ResultsThe results showed significant reduction in serum concentrations of Th1-inducing cytokines IL-12p70 and IFN-γ as well as Th2-related cytokine IL-4 in ACR patients compared with stable controls. However, levels of several Th1-, Th2- and Th17-related cytokines, such as IL-2, TNF-α, TNF-β, IL-12 (p40), IL-10, IL-15, IL-17, IL-21, and IL-23, as well as the frequencies of Th1 and Th17 cell, did not differ between ACR cases and stable controls. Moreover, we found the levels of IFN-γ were correlated with those of the anti-inflammatory factor, IL-1 receptor antagonist (IL-1Ra) in ACR. Notably, the Th1-like Treg cell-to-Foxp3− Th1 cell ratio was significantly lower in ACR patients compared with that in stable controls. In graft biopsies from ACR patients, Treg cells and Th1-like Treg cells were less abundant than those without ACR.ConclusionsOur study indicates that IFN-γ secreted from Th1-like Treg cells negatively modulates ACR.