TGF-β/Smad信号通路在艾滋病患者CD8^＋ T细胞功能损害中的作用

Role of TGF-β/Smad Signaling Pathway in the Impairment of CD8^+ T Cell Function

探讨TGF-β/Smad信号通路在艾滋病患者CD8+T细胞功能损害中的作用。在HIV感染者(CD4+T细胞计数≥200个/μL)和艾滋病病人(CD4+T细胞计数<200个/μL)中各抽取30例,另以30例健康成人为对照。取研究对象的外周静脉血,流式细胞术检测CD8+T细胞CD28分子和磷酸化Smad2/3蛋白(p-Smad2/3),酶联免疫吸附测定法(ELISA)检测血浆中TGF-β1、IFN-γ和TNF-α。健康人、HIV感染者和AIDS病人CD8+CD28+双阳性细胞占CD8+T细胞的比例分别为47.75%、47.40%和36.20%(中位数),AIDS病人低于正常人和HIV感染者(P<0.05);p-Smad2/3阳性CD8+T细胞占CD8+T细胞的比例分别为79.15%、55.60%和60.60%(中位数),HIV感染者和AIDS病人低于健康人(P<0.05);血浆TNF-α分别为(147.92±1.47)pg/mL、(60.04±1.78)pg/mL和(54.43±2.03)pg/mL,HIV感染者和AIDS病人低于健康人(P<0.05);血浆TGF-β1和IFN-γ的组间差异无统计学意义。TGF-β/Smad信号通路可能参与了艾滋病患者CD8+T细胞的异常激活与功能损害。

The present study was designed to explore the role of the transforming growth factor （TGF）-β/ Smad signaling pathway in the impairment of CD8^＋ T cell function. Thirty patients were recruited among HIV infected patients （CD4^＋ T cell counts≥200/μL） and AIDS patients （CD4^＋ T cell counts〈200/μL）, respectively, and thirty healthy people were recruited as controls. Peripheral venous blood was collected from each subject and tested for CD28 molecule and phosphorylated Smad2/3 protein （p-Smad2/3） of CD8^＋ T cells using Flow Cytometry, and for plasma TGF-β1, IFN-γ and TNF-α using enzyme linked immunosorbent assay （ELISA）. CO8^＋ CD28^＋ double-positive ceils accounted for 47. 75%, 47. 40% and 36.20% （median） of the total CD8^＋ T ceils in healthy people, HIV infected patients and AIDS patients, respectively. AIDS patients had a lower proportion of CD8^＋ CD28^＋ double-positive T cells compared with either healthy people or HIV infected patients （P〈0. 05, respectively）. Also, 79. 15%, 55. 60% and 60.60% of CD8^＋ T cells was positive for p-Smad2/3 in healthy people, HIV infected patients and AIDS patients, respectively. This proportion was lower in HIV infected patients and AIDS patients than in healthy people （P〈0.05, respectively）. The plasma level of TNF-α was （147.92± 1.47）pg/mL, （60.04 ±1.78）pg/mL and（54.43±2.03）pg/mL, respectively, in the three groups, and was lower in HIV infected patients and AIDS patients than in healthy people （P〈0.05, respectively）. There were not significant differences in Plasma TGF-β1 and IFN-γ across groups. These data show that the TGF-β/Smad signaling pathway may be involved in abnormal activation and functional impairment of CD8^＋ T cell.