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



To 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.



The 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.



Our study indicates that IFN-γ secreted from Th1-like Treg cells negatively modulates ACR.
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Xiaoguang
X
Xu
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Haiyan
H
Huang
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Qiang
Q
Wang
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Ming
M
Cai
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Yeyong
Y
Qian
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Yong
Y
Han
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Xinying
X
Wang
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Yu
Y
Gao
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Ming
M
Yuan
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Liang
L
Xu
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China.
Chen
C
Yao
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China. Electronic address: xiaolilab309@163.com.
Li
L
Xiao
Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China. Electronic address: shibingyi@medmail.com.cn.
Bingyi
B
Shi
D000208:Acute Disease; D000328:Adult; D064591:Allografts; D015415:Biomarkers; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018121:Receptors, Cytokine / Q000097:blood / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D018121:Receptors, Cytokine; D007371:Interferon-gamma
Acute cellular renal allograft rejection; Interferon-γ; Kidney transplantation; Regulatory t cell