Hirsch Christina S, Johnson John L, Okwera Alphonse, Kanost Richard A, Wu Mianda, Peters Pierre, Muhumuza Mathew, Mayanja-Kizza Harriet, Mugerwa Roy D, Mugyenyi Peter, Ellner Jerrold J, Toossi Zahra
Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio 44106-4984, USA.
J Clin Immunol. 2005 Jul;25(4):353-64. doi: 10.1007/s10875-005-4841-4.
The role of TGF-beta TNF-alpha FasL and Bcl-2 in apoptosis of CD4 T-cells during active TB was studied. Coculture of PBMC from TB patients with neutralizing antibodies to TGF-beta or TNF-alpha decreased spontaneous (P < or = 0.05) and MTB-induced (P < or = 0.02) T-cell apoptosis by 50-90%, but effects were not additive. Interestingly, only levels of TGF-beta in supernatants correlated with rates of spontaneous and MTB-induced apoptosis. FasL surface and mRNA expression were higher in unstimulated and MTB-stimulated PBMC from patients than controls, and neutralization of FasL abrogated apoptosis of T-cells from patients only. Intracellular Bcl-2 protein was lower among unstimulated CD4 T-cells from patients than those from controls (P < or = 0.02), and MTB stimulation reduced intracellular Bcl-2 content in CD4 T-cells from patients only (P < or = 0.001). These findings may indicate that, during TB, predisposition of CD4 T-cells to apoptosis may involve both low expression of Bcl-2, and excessive expression of TGF-beta TNF-alpha and FasL.
研究了转化生长因子-β（TGF-β）、肿瘤坏死因子-α（TNF-α）、Fas配体（FasL）和Bcl-2在活动性结核病期间CD4 T细胞凋亡中的作用。将结核病患者的外周血单核细胞（PBMC）与针对TGF-β或TNF-α的中和抗体共培养，可使自发性（P≤0.05）和结核分枝杆菌（MTB）诱导的（P≤0.02）T细胞凋亡减少50%-90%，但效果无叠加性。有趣的是，仅上清液中TGF-β的水平与自发性和MTB诱导的凋亡率相关。患者未刺激和MTB刺激的PBMC中FasL表面和mRNA表达高于对照组，仅FasL的中和作用可消除患者T细胞的凋亡。患者未刺激的CD4 T细胞中细胞内Bcl-2蛋白低于对照组（P≤0.02），仅MTB刺激可降低患者CD4 T细胞中细胞内Bcl-2含量（P≤0.001）。这些发现可能表明，在结核病期间，CD4 T细胞易于凋亡可能涉及Bcl-2低表达以及TGF-β、TNF-α和FasL的过度表达。
