Tumor necrosis factor is critical for cytolytic T cell activity against allospecific hepatocytes and splenic targets in major histocompatibility complex class I disparate graft versus host disease.
Tumor necrosis factor is critical for cytolytic T cell activity against allospecific hepatocytes and splenic targets in major histocompatibility complex class I disparate graft versus host disease.
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在主要组织相容性复合体 I 类不同移植物抗宿主疾病中，肿瘤坏死因子对于针对同种异体肝细胞和脾靶标的溶细胞 T 细胞活性至关重要。
DOI：
10.1089/jir.2010.0104
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Brown,GeriR
中科院分区：
文献类型：
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作者：
Ali,Sabina;Starwalt,Ruth;Kreck,Jake;Whittington,Bonnie;Brown,GeriR
本研究测定了肿瘤坏死因子（TNF）/肿瘤坏死因子受体（TNFR）相互作用对移植物抗宿主病小鼠脾和肝内淋巴细胞（IHL）细胞溶解（CTL）活性的影响。分别通过4-h51 Cr释放和16-hDNA裂解试验，利用脾细胞（SpC）和分离自（1）接受B6脾和骨髓细胞的亚致死剂量照射的bm 1 × B6 F1的IHL，以及对照腺病毒，评估抗H-2bm 1脾和肝细胞靶点的同种异体杀伤作用（Adv-βgal）或表达TNF抑制剂的腺病毒（2）B6，B6.129-Tnfrsf 1atm 1 Mak/J的bm 1 × B6 F1受体（TNFR 1-/-）、B6. 129 S2-Tnfrsf 1btm 1 Mwm/J（TNFR 2-/-）或B6. 129 S-Tnfrsf 1atm 1 ImxTnfrsf 1btm 1 Imx/J（TNFR-/-）SpC和骨髓细胞，或（3）来自体外激活的SpC。来自在移植时接受Adv-TNFi的骨髓移植受者的脾和IHL显示出比对照低的同种特异性CTL活性。在CTL活性测定之前添加TNFR-Ig或TNF抗体进一步降低了对bm 1 SpC母细胞靶标的同种异体特异性杀伤。TNF/TNFR 1和TNF/TNFR 2相互作用对于开发针对同种异体特异性肝细胞靶标的最佳CTL活性至关重要。此外，TNFR 1和TNFR 2缺陷的SpC从MHC I类不同的混合淋巴细胞培养物显示较低的CTL活性和表达的效应分子比对照B6 SpC。TNF/TNFR相互作用对于IHL和脾细胞毒性T细胞针对MHC I类不同SpC原始细胞和肝细胞靶点的最佳CTL活性的发展至关重要。
The present studies determined the role of tumor necrosis factor (TNF)/tumor necrosis factor receptor (TNFR) interactions on cytolytic (CTL) activity of splenic and intrahepatic lymphocytes (IHL) isolated from mice undergoing graft versus host disease, induced by transfer of B6 T cells to major histocompatibility complex (MHC) class I disparate bm1 × B6 F1 mice. Allospecific killing of anti-H-2bm1splenic and hepatocyte targets was assessed by 4-h51Cr release and 16-h DNA lysis assays, respectively, utilizing spleen cells (SpC) and IHL isolated (1) from sublethally irradiated bm1 × B6 F1 who had received B6 spleen and bone marrow cells, and a control adenovirus (Adv-βgal) or a TNF inhibitor expressing adenovirus (Adv-TNFi), or (2) from bm1 × B6 F1 recipients of B6, B6.129-Tnfrsf1atm1Mak/J (TNFR1−/−), B6.129S2-Tnfrsf1btm1Mwm/J (TNFR2−/−), or B6.129S-Tnfrsf1atm1ImxTnfrsf1btm1Imx/J (TNFR−/−) SpC and bone marrow cells, or (3) fromin vitro-activated SpC. Splenic and IHL from bone marrow transplant recipients who had received Adv-TNFi at the time of transplant displayed lower allospecific CTL activity than controls. Addition of TNFR-Ig or a TNF antibody before the CTL activity assay further reduced allospecific killing against bm1 SpC blast targets. Both TNF/TNFR1 and TNF/TNFR2 interactions were critical for the development of optimal CTL activity against allospecific hepatocyte targets. Further, TNFR1- and TNFR2-deficient SpC from MHC class I disparate mixed lymphocyte cultures displayed lower CTL activity and expression of effector molecules than control B6 SpC. TNF/TNFR interactions were critical for the development of optimal CTL activity of IHL and splenic cytotoxic T cells against MHC class I disparate SpC blast and hepatocyte targets in MHC class I disparate graft versus host disease.