Jasiński M, Wieckiewicz J, Ruggiero I, Pituch-Noworolska A, Zembala M
Department of Clinical Immunology, Polish-American Children's Hospital, Collegium Medicum Jagiellonian University, Cracow.
J Clin Immunol. 1995 Jul;15(4):185-93. doi: 10.1007/BF01541088.
The control of expression of MHC class II molecules on antigen-presenting cells is important for the induction of immunity, while aberrant expression of these molecules plays a role in the immunopathology of autoimmune diseases. This study explored the role of tumor necrosis factor alpha (TNF) in controlling the level of HLA class II mRNA in human monocytes. Exposure of monocytes to exogenous recombinant TNF (rTNF) selectively up-regulated DR alpha-mRNA but not DP or DQ alpha-mRNA. Inhibitors of TNF synthesis, pentoxifylline (PTX) and thalidomide, inhibited TNF mRNA accumulation in LPS-activated monocytes and down-regulated DR mRNA but not DP or DQ mRNA. The inhibitory effect of anti-TNF monoclonal antibody (MAb) indicated that endogenously generated TNF acted extracellularly. Anti-p75 TNF-R2 receptor and to a lesser extent anti-p55 TNF-R1 MAbs inhibited TNF-mediated up-regulation of DR mRNA and TNF mRNA. Taken together, this implies that endogenously generated TNF plays a role in controlling isotype-specific MHC class II gene expression in human monocytes/macrophages. These results may have some implications for anti-tumor response and autoimmunity.
抗原呈递细胞上MHC II类分子表达的调控对于免疫诱导很重要，而这些分子的异常表达在自身免疫性疾病的免疫病理学中起作用。本研究探讨了肿瘤坏死因子α（TNF）在控制人单核细胞中HLA II类mRNA水平方面的作用。将单核细胞暴露于外源性重组TNF（rTNF）可选择性地上调DRα-mRNA，但不影响DP或DQα-mRNA。TNF合成抑制剂己酮可可碱（PTX）和沙利度胺可抑制LPS激活的单核细胞中TNF mRNA的积累，并下调DR mRNA，但不影响DP或DQ mRNA。抗TNF单克隆抗体（MAb）的抑制作用表明内源性产生的TNF在细胞外起作用。抗p75 TNF-R2受体以及程度较轻的抗p55 TNF-R1 MAb可抑制TNF介导的DR mRNA和TNF mRNA的上调。综上所述，这意味着内源性产生的TNF在控制人单核细胞/巨噬细胞中同种型特异性MHC II类基因表达方面起作用。这些结果可能对抗肿瘤反应和自身免疫有一些启示。
