Freishtat Robert J, Mitchell Lindsay W, Ghimbovschi Svetlana D, Meyers Samuel B, Hoffman Eric P
Division of Emergency Medicine, Children's National Medical Center, and Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC 20010-2970, USA.
Hum Immunol. 2005 Dec;66(12):1223-34. doi: 10.1016/j.humimm.2006.02.005. Epub 2006 Mar 27.
NKG2A is commonly expressed on cytotoxic cells but has been found on activated T helper (TH) cells. In identifying novel markers differentiating between TH1 and TH2 lymphocytes, we focused on NKG2A expression. TH1 and TH2 cells were negatively isolated from healthy volunteers for microarray analysis and reverse transcription polymerase chain reaction (RT-PCR). Flow cytometry of quiescent and activated TH1 and TH2 cells was performed. Isolates were >95% pure CD3+CD4+ cells (TH1=90.3% and TH2=84.1%). Microarrays revealed differential expression of NKG2A and NKG2C isoforms between TH1 and TH2 cells. RT-PCR indicated greater expression of NKG2A in TH2 cells (4-fold) and NKG2C in TH1 cells (3-fold). Flow studies revealed tripling of TH2 NKG2A with activation to 10.76+/-4.01% (p=0.05), a 23-fold increase in CD56 to 35+/-14.54% (p=0.03), and an increase in NKG2A+CD56+ double-positive cells to 3.04+/-1.38% (p=0.04). TH1 lymphocytes did not differ with activation. We identified co-induction of NKG2A and CD56 on activation of TH2 cells. These cells would likely bind more HLA-E and exhibit increased effector inhibition. Given that certain viruses are known to decrease MHC class I and thus HLA-E production by antigen-presenting cells, activated TH2 cells would bind less HLA-E in this scenario. This would likely result in less effector inhibition and a relatively robust TH2 response.
NKG2A通常在细胞毒性细胞上表达，但也在活化的辅助性T（TH）细胞上被发现。在鉴定区分TH1和TH2淋巴细胞的新型标志物时，我们关注了NKG2A的表达。从健康志愿者中阴性分离出TH1和TH2细胞用于微阵列分析和逆转录聚合酶链反应（RT-PCR）。对静止和活化的TH1和TH2细胞进行了流式细胞术检测。分离出的细胞为纯度>95%的CD3+CD4+细胞（TH1=90.3%，TH2=84.1%）。微阵列显示TH1和TH2细胞之间NKG2A和NKG2C异构体存在差异表达。RT-PCR表明TH2细胞中NKG2A表达更高（4倍），TH1细胞中NKG2C表达更高（3倍）。流式研究显示，活化后TH2细胞的NKG2A增加两倍，达到10.76+/-4.01%（p=0.05），CD56增加23倍，达到35+/-14.54%（p=0.03），NKG2A+CD56+双阳性细胞增加至3.04+/-1.38%（p=0.04）。TH1淋巴细胞活化后无差异。我们发现TH2细胞活化时NKG2A和CD56共同诱导。这些细胞可能会结合更多的HLA-E并表现出增强的效应抑制。鉴于已知某些病毒会降低MHC I类分子，从而减少抗原呈递细胞产生的HLA-E，在这种情况下活化的TH2细胞会结合较少的HLA-E。这可能会导致效应抑制减少和相对较强的TH2反应。
