Brown G R, Thiele D L
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75390-9151, USA.
Eur J Immunol. 2000 Oct;30(10):2900-7. doi: 10.1002/1521-4141(200010)30:10<2900::AID-IMMU2900>3.0.CO;2-P.
In vivo TNF inhibition has been observed to ameliorate the disease process attributed to T cell-dependent immune responses such as those generated during graft-vs.-host disease. The present studies were designed to evaluate whether TNF/TNF receptor (TNFR)1 and TNF/TNFR2 interactions were involved in the generation of allospecific T cell responses. Splenic lymphocyte populations were obtained from TNFR1- or TNFR2-deficient B6 mice and from control B6 mice. These responder cells were cultured with irradiated MHC class II-disparate B6.C-H-2bm12 (bm12) or MHC class I-disparate B6.C-H-2bm1 (bm1) or irradiated syngeneic stimulator cells for 3 days before assay of [3H]thymidine incorporation. IL-2 levels of the mixed lymphocyte culture (MLC) supernatants were assessed by enzyme-linked immunosorbent assay. With MHC class II-disparate bm12 stimulator cells, a significant reduction in T cell proliferation was observed utilizing TNFR2-deficient CD4+ responder T cells, but not when using TNFR1 -deficient CD4+ responder T cells. A significant decrease in proliferation of TNFR1-deficient CD8+ responder cells, but not of TNFR2-deficient CD8 responder T cells was observed after stimulation with MHC class I-disparate bm1 stimulator cells. IL-2 levels were lower in MLC utilizing MHC class I stimulators and TNFR1-deficient responders or MHC class II stimulators and TNFR2-deficient responders. These results indicate that TNF/TNFR2 interactions promote MHC class II-stimulated alloresponses, while TNF/TNFR1 interactions promote MHC class I-stimulated alloresponses.
体内肿瘤坏死因子（TNF）抑制已被观察到可改善归因于T细胞依赖性免疫反应的疾病进程，例如移植物抗宿主病期间产生的免疫反应。本研究旨在评估TNF/肿瘤坏死因子受体（TNFR）1和TNF/TNFR2相互作用是否参与同种异体特异性T细胞反应的产生。从TNFR1或TNFR2缺陷的B6小鼠以及对照B6小鼠中获取脾淋巴细胞群体。在检测[3H]胸腺嘧啶核苷掺入之前，将这些反应细胞与经照射的MHC II类不相合的B6.C-H-2bm12（bm12）或MHC I类不相合的B6.C-H-2bm1（bm1）或经照射的同基因刺激细胞培养3天。通过酶联免疫吸附测定法评估混合淋巴细胞培养（MLC）上清液中的白细胞介素-2水平。对于MHC II类不相合的bm12刺激细胞，利用TNFR2缺陷的CD4+反应性T细胞时观察到T细胞增殖显著降低，但使用TNFR1缺陷的CD4+反应性T细胞时未观察到这种情况。在用MHC I类不相合的bm1刺激细胞刺激后，观察到TNFR1缺陷的CD8+反应性细胞增殖显著降低，但TNFR2缺陷的CD8反应性T细胞未出现这种情况。在利用MHC I类刺激物和TNFR1缺陷的反应细胞或MHC II类刺激物和TNFR2缺陷的反应细胞的MLC中，白细胞介素-2水平较低。这些结果表明，TNF/TNFR2相互作用促进MHC II类刺激的同种异体反应，而TNF/TNFR1相互作用促进MHC I类刺激的同种异体反应。
