CMV感染性肝炎患儿外周血T淋巴细胞的水平及意义
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摘要
目的分析巨细胞病毒(CMV)感染致肝炎患儿外周血CD3、CD4、CD8和CD4/CD8T淋巴细胞水平及其与CMV载量的相关性。方法选取2016年3月至2018年3月在余姚市第二人民医院就诊的65例CMV感染致肝炎患儿为病例组,根据其CMV载量水平的不同,分为低载量组(CMV<1×104拷贝/mL)、中载量组(CMV为1×104～<5×104拷贝/mL)、高载量组(CMV为5×104～10×104拷贝/mL),另选取同期30例体检健康儿童为对照组。比较病例组与对照组外周血T淋巴细胞亚群(CD3、CD4、CD8和CD4/CD8)的含量,并比较不同CMV载量亚组患儿外周血T淋巴细胞亚群的水平,采用Pearson相关性分析CMV感染致肝炎患儿CMV载量与外周血T淋巴细胞亚群水平的关系。结果病例组患儿外周血CD3、CD4及CD4/CD8的水平较对照组均显著降低(t值分别为5.99、5.80、7.32,均P<0.01);而两组CD8水平比较并无明显差异(t=0.84,P>0.05)。低载量组外周血CD3、CD4及CD4/CD8水平较中载量组均显著升高(q值分别为10.12、4.63、6.85,均P<0.05),较高载量组亦均显著升高(q值分别为15.96、7.68、7.95,均P<0.05),中载量组外周血CD3、CD4及CD4/CD8水平较高载量组均显著升高(q值分别为11.05、7.36、7.84,均P<0.05);而三组CD8水平比较,并无明显差异(F=1.84,P>0.05)。经Pearson相关性分析显示,CMV载量与CD3、CD4及CD4/CD8均呈负相关(r值分别为-0.58、-0.53、-0.73,均P<0.01),而与CD8并无明显关系(r=0.10,P>0.05)。结论 CMV感染致肝炎患儿机体免疫功能受损,且CMV可阻滞外周血T淋巴细胞亚群中CD3与CD4细胞增殖,而对CD8淋巴细胞的影响较小,故临床中应及时测定肝炎患儿外周血T淋巴细胞亚群,尤其是CD3和CD4的表达水平。
Objective To analyze the levels of T lymphocytes such as CD3,CD4,CD8 and CD4/CD8 in peripheral blood of children with hepatitis caused by cytomegalovirus(CMV)infection and correlation with CMV load.Methods From March 2016 to March2018,65 children with hepatitis caused by CMV infection in the Second People's Hospital of Yuyao were selected in case group and divided into low-load group(CMV < 1×104 copies/mL),medium-load group(CMV ranged 1×104-5×104 copies/mL)and high-load group(CMV ranged 5×104-10×104 copies/mL)according to the CMV load levels.Another 30 cases of healthy children for physical examination were selected at the same time as control group.The levels of peripheral blood T lymphocyte subsets(CD3,CD4,CD8 and CD4/CD8)were compared between case group and control group,and the expression levels of T lymphocyte subsets in peripheral blood of children with different CMV load subgroups were compared.Pearson correlation analysis was used to analyze the correlation between CMV load and the expression level of peripheral blood T lymphocyte subsets in children with hepatitis caused by CMV infection.Results The levels of CD3,CD4 and CD4/CD8 in peripheral blood of the case group were significantly lower than those in the control group(t value was 5.99,5.80 and 7.32 respectively,all P<0.01),but the levels of CD8 in two groups showed no significant difference(t=0.84,P>0.05).The levels of CD3,CD4 and CD4/CD8 in peripheral blood of low-load group were significantly higher than those in medium-load group(q value was 10.12,4.63 and 6.85,respectively,all P<0.05),and they were also significantly higher than those in high-load group(q value was 15.96,7.68 and 7.95,respectively,all P<0.05).The levels of CD3,CD4 and CD4/CD8 in peripheral blood of medium-load group were significantly higher than those in high-load group(q value was 11.05,7.36 and 7.84,respectively,all P<0.05).There was no significant difference in the levels of CD8 among three groups(F=1.84,P>0.05).Pearson correlation analysis showed that CMV load was negatively correlated with CD3,CD4 and CD4/CD8(r value was-0.58,-0.53 and-0.73,respectively,all P<0.01),but showed no correlation with CD8(r=0.10,P>0.05).Conclusion The immune function of children with hepatitis caused by CMV infection is impaired.CMV can block the proliferation of T lymphocyte subsets such as CD3 and CD4 cells in peripheral blood,but has little effect on CD8 lymphocytes.Therefore,it is necessary to detect the levels of T lymphocyte subsets of peripheral blood in children with hepatitis,especially the levels of CD3 and CD4 cells.
Objective To analyze the levels of T lymphocytes such as CD3,CD4,CD8 and CD4/CD8 in peripheral blood of children with hepatitis caused by cytomegalovirus(CMV)infection and correlation with CMV load.Methods From March 2016 to March2018,65 children with hepatitis caused by CMV infection in the Second People's Hospital of Yuyao were selected in case group and divided into low-load group(CMV < 1×104 copies/mL),medium-load group(CMV ranged 1×104-5×104 copies/mL)and high-load group(CMV ranged 5×104-10×104 copies/mL)according to the CMV load levels.Another 30 cases of healthy children for physical examination were selected at the same time as control group.The levels of peripheral blood T lymphocyte subsets(CD3,CD4,CD8 and CD4/CD8)were compared between case group and control group,and the expression levels of T lymphocyte subsets in peripheral blood of children with different CMV load subgroups were compared.Pearson correlation analysis was used to analyze the correlation between CMV load and the expression level of peripheral blood T lymphocyte subsets in children with hepatitis caused by CMV infection.Results The levels of CD3,CD4 and CD4/CD8 in peripheral blood of the case group were significantly lower than those in the control group(t value was 5.99,5.80 and 7.32 respectively,all P<0.01),but the levels of CD8 in two groups showed no significant difference(t=0.84,P>0.05).The levels of CD3,CD4 and CD4/CD8 in peripheral blood of low-load group were significantly higher than those in medium-load group(q value was 10.12,4.63 and 6.85,respectively,all P<0.05),and they were also significantly higher than those in high-load group(q value was 15.96,7.68 and 7.95,respectively,all P<0.05).The levels of CD3,CD4 and CD4/CD8 in peripheral blood of medium-load group were significantly higher than those in high-load group(q value was 11.05,7.36 and 7.84,respectively,all P<0.05).There was no significant difference in the levels of CD8 among three groups(F=1.84,P>0.05).Pearson correlation analysis showed that CMV load was negatively correlated with CD3,CD4 and CD4/CD8(r value was-0.58,-0.53 and-0.73,respectively,all P<0.01),but showed no correlation with CD8(r=0.10,P>0.05).Conclusion The immune function of children with hepatitis caused by CMV infection is impaired.CMV can block the proliferation of T lymphocyte subsets such as CD3 and CD4 cells in peripheral blood,but has little effect on CD8 lymphocytes.Therefore,it is necessary to detect the levels of T lymphocyte subsets of peripheral blood in children with hepatitis,especially the levels of CD3 and CD4 cells.
引文
[1]向正可,谭从容.更昔洛韦联合培菲康治疗小儿巨细胞病毒性肝炎的疗效及抗病毒效果分析[J].中国妇幼健康研究,2017,28(3):282-284.
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[5]Naik S,Nicholas S K,Martinez C A,et al.Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes[J].J Aller Clini Immunol,2016,137(5):1498-1505.
[6]Neuenhahn M,Albrecht J,Odendahl M,et al.Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT[J].Leukemia,2017,31(10):2161.
[7]Yu W,Jiang N,Ebert P J R,et al.Clonal deletion prunes but does not eliminate self-specificαβCD8+Tlymphocytes[J].Immunity,2015,42(5):929-941.
[8]Schlums H,Cichocki F,Tesi B,et al.Cytomegalovirus infection drives adaptive epigenetic diversification of NKcells with altered signaling and effector function[J].Immunity,2015,42(3):443-456.
[2]Leonardsson H,Hreinsson J P,L9ve A,et al.Hepatitis due to Epstein-Barr virus and cytomegalovirus:clinical features and outcomes[J].Scand J Gastroenterol,2017,52(8):893-897.
[3]Uslu U,Agaimy A,Hundorfean G,et al.Autoimmune colitis and subsequent CMV-induced hepatitis after treatment with ipilimumab[J].J Immunother,2015,38(5):212-215.
[4]Kah J,Koh S,Volz T,et al.Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection[J].J Clin Invest,2017,127(8):3177-3188.
[5]Naik S,Nicholas S K,Martinez C A,et al.Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes[J].J Aller Clini Immunol,2016,137(5):1498-1505.
[6]Neuenhahn M,Albrecht J,Odendahl M,et al.Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT[J].Leukemia,2017,31(10):2161.
[7]Yu W,Jiang N,Ebert P J R,et al.Clonal deletion prunes but does not eliminate self-specificαβCD8+Tlymphocytes[J].Immunity,2015,42(5):929-941.
[8]Schlums H,Cichocki F,Tesi B,et al.Cytomegalovirus infection drives adaptive epigenetic diversification of NKcells with altered signaling and effector function[J].Immunity,2015,42(3):443-456.