Regulation of the CTL response by macrophage migration inhibitory factor
Regulation of the CTL response by macrophage migration inhibitory factor
复制标题
DOI：
10.4049/jimmunol.166.2.747
复制
发表时间：
2001-01-15
影响因子：
4.4
通讯作者：
Metz, CN
中科院分区：
文献类型：
--
作者：
Abe, R;Peng, T;Metz, CN
巨噬细胞移动抑制因子（MIF）已被证明是介导宿主炎症和免疫反应的关键细胞因子。最近，已发现MIF的免疫中和作用可抑制小鼠肿瘤生长;然而，这种作用的潜在机制尚未得到很好的定义。我们研究了MIF是否在CTL活性的表达中起调节作用。在使用OVA转染的肿瘤细胞系EL 4（EG.7）的CTL应答的小鼠模型中，我们发现从EG.7致敏小鼠获得的脾细胞培养物在体外Ag刺激后分泌高水平的MIF。值得注意的是，与对照mAb处理的培养物相比，用中和性抗MIF mAb处理的平行脾细胞培养物显示针对EG.7细胞的CTL应答显著增加。这种效应伴随着IFN-γ表达的升高。抗-MIF处理动物的EG.7肿瘤的组织学检查显示CD 4（+）和CD 8（+）T细胞以及凋亡肿瘤细胞显著增加，这与抗-MIF在体内观察到的CTL活性增强一致。这种CTL活性的增加与IL-2 R的共同γ（c）链的表达增强有关，该γ（c）链介导CD 8（+）T细胞存活。最后，从抗MIF处理的EG.7荷瘤小鼠脾脏中获得的CD 8（+）T淋巴细胞，当转移到受体荷瘤小鼠中时，显示肿瘤组织中的积累增加。这些数据提供了第一个证据的一个重要作用，MIF在体内的调节和运输的抗肿瘤T淋巴细胞。
Macrophage migration inhibitory factor (MIF) has been shown to be a pivotal cytokine that mediates host inflammatory and immune responses. Recently, immunoneutralization of MIF has been found to inhibit tumor growth in mice; however, the contributing mechanisms underlying this effect have not been well defined. We investigated whether MIF plays a regulatory role in the expression of CTL activity. In a mouse model of the CTL response using the OVA-transfected tumor cell line EL4 (EG.7), we found that cultures of splenocytes obtained from EG.7-primed mice secrete high levels of MIF following Ag stimulation in vitro. Notably, parallel splenocyte cultures treated with neutralizing anti-MIF mAb showed a significant increase in the CTL response directed against EG.7 cells compared with control mAb-treated cultures. This effect was accompanied by elevated expression of IFN-gamma. Histological examination of the EG.7 tumors from anti-MIF-treated animals showed a prominent increase in both CD4(+) and CD8(+) T cells as well as apoptotic tumor cells, consistent with the observed augmentation of CTL activity in vivo by anti-MIF. This increased CTL activity was associated with enhanced expression of the common gamma (c)-chain of the IL-2R that mediates CD8(+) T cell survival. Finally, CD8(+) T lymphocytes obtained from the spleens of anti-MIF-treated EG.7 tumor-bearing mice, when transferred into recipient tumor-bearing mice, showed increased accumulation in the tumor tissue. These data provide the first evidence of an important role for MIF in the regulation and trafficking of anti-tumor T lymphocytes in vivo.