Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro.
Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro.
复制标题
来自 lpr 小鼠的异常 T 细胞在体外下调干扰素-γ 和肿瘤坏死因子-α 的转录。
作者：
Lesley J. Murray;C. Martens
我们已经研究了分离的T细胞亚群的自身免疫性小鼠MRL/MPJ/lpr/lpr（lpr）的增殖能力，并在体外细胞因子基因转录的变化，在存在或不存在的细胞因子。由于异常的CD 4-/CD 8- T淋巴细胞的积累，lpr小鼠出现狼疮样症状和大量淋巴结病，这在共表达Thy 1和B220中是不寻常的。FACS纯化的B220+/Thy 1 + lpr淋巴结细胞对细胞因子几乎没有增殖反应，即使在PMA存在的情况下也是如此，并且不能响应于通过CD 3/TcR复合物的刺激而增殖。聚合酶链反应用于检测体外培养前后B220-/Thy 1+和B220+/Thy 1+（“异常”）T细胞中细胞因子基因转录物的存在。在新鲜分离的B220+/Thy 1+细胞中观察到的IFN-γ和TNF-α基因的高水平转录物在体外培养10小时后下降，而TNF-β、IL-6和TGF-β转录物的水平保持不变。这些结果表明，IFN-γ和TNF-α基因转录的lpr B220+/Thy 1+细胞的阳性刺激可能存在于体内，但在纯化该异常T细胞亚群后被去除。
We have studied the ability of isolated T cell subpopulations from the autoimmune mouse MRL/MPJ/lpr/lpr (lpr) to proliferate and to undergo changes in cytokine gene transcription in vitro, in the presence or absence of cytokines. The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220. FACS-purified B220+/Thy1+ lpr lymph node cells showed little proliferative response to cytokines, even in the presence of PMA, and failed to proliferate in response to stimulation through the CD3/TcR complex. Polymerase chain reaction was used to examine the presence of cytokine gene transcripts in B220-/Thy1+ and B220+/Thy1+ ("abnormal") T cells, before and after in vitro culture. The high level of transcripts of IFN-gamma and TNF-alpha genes observed in freshly isolated B220+/Thy1+ cells decreased after 10 hr of in vitro culture, while levels of TNF-beta, IL-6 and TGF-beta transcripts were maintained. These results suggest that a positive stimulus for IFN-gamma and TNF-alpha gene transcription by lpr B220+/Thy1+ cells may exist in vivo but is removed upon purification of this abnormal T cell subset.