NKG2D受体和配体的表达及在HIV-1感染中的临床意义

发布时间：2018-01-14 01:16

本文关键词：NKG2D受体和配体的表达及在HIV-1感染中的临床意义　出处：《中南大学》2013年硕士论文　论文类型：学位论文

【摘要】：背景：人类免疫缺陷病毒(human immunodeficiency virus, HIV)主要通过侵犯人体的免疫细胞,引起CD4+T淋巴细胞数量进行性减少和多种免疫细胞量和质的改变使得人体细胞免疫功能缺陷,导致艾滋病(acquired immure deficiency syndrome, AIDS)及各种机会感染、肿瘤的发生。高效抗反转录病毒治疗(highly active antiretroviral therapy, HAART)能持续降低体内HIV数量,重建免疫系统,控制机会性感染、延缓病情进展、减少疾病传播,进而提高患者的生活治疗。NKG2D是一种C型凝集素样活化型受体,具有高度保守性,主要表达于NK细胞、NKT细胞、CD8+T淋巴细胞、γδT细胞及某些状态下的CD4+T淋巴细胞表面。近年来,NKG2D配体相继被发现,NKG2D配体具有惊人的多态性,且与MHCI分子差异性很大。本文将国内首次研究NKG2D受体和配体表达及其在HIV-1感染中的临床意义,HAART对NKG2D受体和配体表达的影响。目的：研究外周血NK细胞表面NKG2D受体和CD4+T淋巴细胞表面NKG2D配体ULBP1、ULBP2的表达及其在HIV-1感染中的临床意义；HAART对NKG2D受体和配体ULBP1、ULBP2表达的影响,进一步探索艾滋病的发病机制及免疫重建机制。方法：随机选取16例健康志愿者(NC组)；未经HAART的HIV-1组(HIV组)15例,未经HAART的AIDS组(AIDS组)20例及经严格的HAART1年组(HAART组)14例。密度梯度离心法从外周静脉血中分离单个核细胞(PBMC),磁珠分选出NK细胞(CD56P日性细胞)和CD4+T淋巴细胞(CD3阳性CD4阳性细胞),流式细胞术检测NK细胞表面NKG2D的表达水平,CD4+T淋巴细胞表面ULBP1、ULBP2配体的表达水平和ULBP1/ULBP2双阳性细胞表达水平,同时检测CD4+T淋巴细胞绝对计数与上述各项指标的相关性。结果：HIV感染后NK细胞表面NKG2D表达水平低于健康对照,随着疾病的进展,这种差异更明显,高效抗逆转录病毒治疗可以提高NKG2D表达。其中,HIV组低于NC组,AIDS组低于HIV组,]3AART组高于AIDS组。HIV感染后CD4+T淋巴细胞表面ULBP1、ULBP2表达水平上升,随着疾病的进展,这种上升更明显,高效抗逆转录病毒治疗可以逆转这种上升。其中HIV组高于NC组,AIDS组高于HIV组,HAART组低于AIDS组。CD4+T淋巴细胞绝对数与NK细胞表面的NKG2D和CD4+T淋巴细胞表面ULBP1、ULBP2的表达存在相关关系。同时NKG2D与ULBP1、ULBP2存在相关关系。结论：1.国内首次观察到HIV感染者外周血NK细胞表面NKG2D受体表达水平较正常人明显降低,CD4+T淋巴细胞表面的NKG2D配体ULBP1和ULBP2表达较正常人明显升高,三者的变化随病情进展(AIDS组)更显著,且其变化与CD4+T淋巴细胞绝对计数存在相关关系；此外NK细胞表面NKG2D表达与CD4+T淋巴细胞表面ULBP1、ULBP2表达存在相关关系,提示NK细胞表面的NKG2D受体和CD4+T淋巴细胞表面的ULBP1、ULBP2均参与了HIV感染的免疫病理过程和免疫发病机制,且存在相互作用。2.首次观察到HIV感染者尤其AIDS患者,外周血CD4+T淋巴细胞表面ULBP1/ULBP2双阳性细胞表达较正常人升高,随病情进展其变化更显著,且其表达与对应的CD4+T淋巴细胞绝对计数及NK细胞表面NKG2D的表达存在相关关系。3.首次观察到HIV感染者外周血NK细胞表面NKG2D受体水平、CD4+T淋巴细胞表面ULBP1和ULBP2配体水平及ULBP1/ULBP2双阳性细胞表达水平的变化,经过一年的HAART可以部分纠正这种变化,且与其对应的CD4+T淋巴细胞绝对计数存在对应关系,提示上述四者均可能参与了HIV感染者抗病毒治疗的免疫重建过程。
[Abstract]:Background: human immunodeficiency virus (human immunodeficiency, virus, HIV) mainly through violations of human immune cells induced by CD4+T lymphocyte number were decreased and the immune cell quantity and quality because of the change of cellular immune function of the human body defects, which causes AIDS (acquired immure deficiency syndrome, AIDS) and a variety of opportunistic infections, cancer. High anti anti retroviral therapy (highly active antiretroviral therapy, HAART) can continue to reduce the amount of HIV in the body, the reconstruction of the immune system to control opportunistic infections, delay the progress of the disease, reduce the spread of the disease, and improve the life for the treatment of patients with.NKG2D is a kind of C type lectin like receptor activation, is highly conservative, mainly expressed in NK cells, NKT cells, CD8+T lymphocytes, CD4+T lymphocytes and T cells in some conditions. In recent years, NKG2D ligands have been It is found that the NKG2D ligand has amazing polymorphism and is quite different from MHCI molecule. In this paper, we first studied the expression of NKG2D receptor and ligand and its clinical significance in HIV-1 infection, and the effect of HAART on NKG2D receptor and ligand expression.
Objective: To study the NK cell surface in the peripheral blood NKG2D lymphocyte surface NKG2D receptor and CD4+T ligand ULBP1, ULBP2 expression and its clinical significance in patients with HIV-1 infection; HAART of NKG2D receptor and ligand ULBP1, ULBP2 expression, to further explore the pathogenesis of AIDS and immune reconstitution mechanism.
Methods: 16 healthy volunteers (NC group); HIV-1 group without HAART (group HIV) 15 cases, AIDS group without HAART (AIDS group) and 20 cases by strict HAART1 group (HAART group) 14 cases. The mononuclear cells were isolated from peripheral blood by density gradient centrifugal method (PBMC), magnetic beads selected NK cells (CD56P cells) and CD4+T cells (CD3 positive CD4 positive cells), detection of the expression levels of NK cell surface NKG2D flow cytometry, CD4+T lymphocyte ULBP1, ULBP1/ULBP2 expression and ULBP2 ligand expression of double positive cells, at the same time the correlation between CD4+T lymphocyte the absolute count and the above indexes.
Results: HIV infected NK cell surface expression level of NKG2D was lower than the control, with the progress of the disease, the difference is more obvious, highly active antiretroviral therapy can improve the expression of NKG2D. Among them, HIV group than in NC group, AIDS group than in HIV group,]3AART group than in AIDS group.HIV after CD4+T infected ULBP1 cell surface expression. The level of ULBP2 increased with the progression of the disease, this rise is more obvious, highly active antiretroviral therapy can reverse the rise. In the HIV group than in the NC group, AIDS group than in HIV group, HAART group,.CD4+T AIDS group was lower than the absolute lymphocyte count and NK cell surface NKG2D and CD4+T ULBP1 lymphocytes, the relationship between the expression of ULBP2 at the same time. NKG2D and ULBP1, the relationship between ULBP2.
Conclusion: the expression of 1. domestic first observed in HIV infected peripheral blood NK cell surface NKG2D receptor levels were decreased significantly, the surface of CD4+T lymphocyte NKG2D ligand ULBP1 and ULBP2 expression were significantly higher than the normal, the changes of the three with the progress of the disease (AIDS group) is more significant, the relationship between the changes of CD4+T and absolute lymphocyte count; in addition NK cell surface expression of NKG2D and CD4+T lymphocytes ULBP1, the relationship between the expression of ULBP2, suggesting that NK cell surface receptor NKG2D and CD4+T lymphocytes ULBP1, ULBP2 are involved in the immunopathology of HIV infection and immune pathogenesis, and the interaction between.2. first observed HIV infection especially AIDS patients expressed higher than normal person ULBP1/ULBP2 on the surface of CD4+T lymphocytes in peripheral blood of double positive cells, with the progression of the more significant changes, and the expression and corresponding The expression of the absolute counts of CD4+T lymphocyte and NK cell surface NKG2D is related to.3. infection were observed for the first time HIV level of peripheral blood NK cell surface NKG2D receptor, the expression of double positive cells CD4+T ULBP1 lymphocytes and ULBP2 ligand level and ULBP1/ULBP2, after a year of HAART can partially correct for this change, there is a corresponding relationship between and the corresponding CD4+T absolute lymphocyte count, suggesting that the four may be involved in the antiviral treatment of HIV infected immune reconstitution process.

【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.91

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