免疫调控受体PD-1和TIGIT在HIV感染者/HIV患者CD3^+CD4^-T细胞表达研究

The expression of immune checkpoint receptors PD-1 and TIGIT on CD3^+CD4^-T cells in untreated HIV infected/AIDS individuals

深入了解免疫调控受体程序性死亡分子1(programmed death 1,PD-1)和T细胞免疫球蛋白及免疫酪氨酸样抑制基序(T cell immunoglobulin and ITIM domain,TIGIT)在人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者/HIV患者外周血CD3^+CD4^-T细胞的表达情况及其与疾病进展的关系。用流式细胞仪检测24例未治疗的HIV感染者/HIV患者外周血CD3^+CD4^-T细胞表面PD-1和TIGIT的表达百分比、CD4+T细胞绝对值计数,实时荧光定量PCR检测HIV病毒载量,并与20例HIV抗体阴性者表达情况比较(HIV-negative normal control,NC)。结果发现HIV感染者/HIV患者CD3^+CD4^-T细胞表面TIGIT受体表达百分数较健康对照组明显增高(P<0.000 1),与CD4+T细胞绝对计数呈负相关(r=-0.450 4,P=0.027 1),与病毒载量呈正相关(r=0.621 4,P=0.001 2);HIV感染者CD3^+CD4^-T细胞PD-1受体表达百分数较健康对照组明显增高(P<0.000 1),与CD4+T细胞绝对计数呈负相关(r=-0.455,P=0.0255);PD-1和TIGIT共表达的CD3^+CD4^-T细胞百分数在HIV感染者/HIV患者中表达明显增高(P<0.000 1)。HIV感染机体后,CD3^+CD4^-T细胞PD-1受体和TIGIT受体表达百分数均明显增高,且与HIV疾病进展密切相关。

To better understand the alteration of immune checkpoint receptors PD-1（programmed death 1）and TIGIT（T cell immunoglobulin and ITIM domains）expressed on CD3^＋CD4^-T cells of untreated HIV infected/AIDS individuals,peripheral blood was taken from 24 normal controls with negative HIV antibody（NC group）and 20 untreated HIV infected individuals（HIV group）.The expressions of PD-1 and TIGIT on the surface of CD3^＋CD4^-T cells were analyzed by flow cytometer.And then CD4＋T cells were counted and viral load was tested by RT-qPCR.We found that the expression of TIGIT on CD3^＋CD4^-T cells in HIV group was significantly higher than that in the NC group（P〈0.000 1）.Furthermore,the expression of TIGIT on CD3^＋CD4^-T cells was negatively correlated with the absolute number of CD4＋T cells（r=-0.450 4,P=0.027 1）,but positively correlated with the viral load（r=0.621 4,P=0.001 2）.On the other hand,compared with the controls,the expression of PD-1 on CD3^＋CD4^-T cells in HIV group was significantly increased（P〈0.000 1）,and it was negatively correlated with the absolute number of CD4＋T cells（r=-0.455 0,P=0.025 5）.Also,the ratio of CD3^＋CD4^-T cells that were double positive for TIGIT and PD-1 in HIV group was also significantly higher than that in the NC group（P〈0.000 1）.In conclusion,the expressions of PD-1 and TIGIT on CD3^＋CD4^-T cells in HIV infected/AIDS individuals significantly increased and correlated with HIV disease progression.