Wild Clarissa Anni, Brandau Sven, Lindemann Monika, Lotfi Ramin, Hoffmann Thomas K, Lang Stephan, Bergmann Christoph
Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr 55, 45122 Essen, Germany.
Arch Otolaryngol Head Neck Surg. 2010 Dec;136(12):1253-9. doi: 10.1001/archoto.2010.195.
to investigate the role of Toll-like receptor (TLR) signaling and T-regulatory (T-reg) cells in patients with head and neck squamous cell carcinoma (HNSCC).
multicolor flow cytometry was used to study the frequency and phenotype of CD4(+)CD25(+)CD127(-) T-reg cells and CD4(+)CD25(-)CD127(+) T-effector (T-eff) cells in peripheral blood mononuclear cells (PBMCs).
all patients were seen at the outpatient clinic at the Department of Otorhinolaryngology at the University of Duisburg-Essen from March 1, 2009, through December 31, 2009.
eleven patients with HNSCC and 10 healthy donors (HDs) were studied. T-reg and T-eff cells were isolated from PBMCs using a magnetic bead-activated cell-sorting technique.
proliferation of T-eff cells and suppressor activity of T-reg cells were assessed in functional assays after preincubation with the TLR4 ligand heat shock protein 60 or lipopolysaccharide in the presence or absence of neutralizing antibody against TLR4.
frequency of T-reg cells in PBMCs was strongly increased in patients with HNSCC vs HDs. Isolation of T-reg cells from PBMCs of patients with HNSCC showed a significantly higher expression of TLR4, TLR6, TLR9, and TLR10 compared with HDs, whereas TLR2 was not detectable. After incubation with heat shock protein 60 or lipopolysaccharide, the suppressive function of T-reg cells was significantly increased (1.14- and 1.44-fold, respectively), whereas the proliferation capacity of T-eff cells remained unchanged. This effect was reversed after TLR4 inhibition on T-reg cells.
the TLR ligation on T-reg cells may contribute to tumor-mediated immune suppression by enhancing their suppressive activity.
探讨Toll样受体（TLR）信号传导及调节性T细胞（T-reg）在头颈部鳞状细胞癌（HNSCC）患者中的作用。
采用多色流式细胞术研究外周血单个核细胞（PBMC）中CD4(+)CD25(+)CD127(-) T-reg细胞及CD4(+)CD25(-)CD127(+) T效应（T-eff）细胞的频率及表型。
2009年3月1日至2009年12月31日期间，所有患者均在杜伊斯堡-埃森大学耳鼻喉科门诊就诊。
研究了11例HNSCC患者及10名健康供者（HD）。采用磁珠激活细胞分选技术从PBMC中分离T-reg细胞和T-eff细胞。
在有或无抗TLR4中和抗体存在的情况下，将T-eff细胞与TLR4配体热休克蛋白60或脂多糖预孵育后，通过功能试验评估T-eff细胞的增殖及T-reg细胞的抑制活性。
与HD相比，HNSCC患者PBMC中T-reg细胞频率显著增加。从HNSCC患者PBMC中分离的T-reg细胞显示，与HD相比，TLR4、TLR6、TLR9和TLR10的表达显著更高，而未检测到TLR2。与热休克蛋白60或脂多糖孵育后，T-reg细胞的抑制功能显著增强（分别为1.14倍和1.44倍），而T-eff细胞的增殖能力保持不变。对T-reg细胞进行TLR4抑制后，该效应逆转。
T-reg细胞上的TLR连接可能通过增强其抑制活性而导致肿瘤介导的免疫抑制。
