本文關(guān)鍵詞：NKG2D受體和配體的表達(dá)及在HIV-1感染中的臨床意義　出處：《中南大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 人免疫缺陷病毒 NKG2D ULBP HAART 流式細(xì)胞術(shù) 磁珠分選

【摘要】：背景：人類免疫缺陷病毒(human immunodeficiency virus, HIV)主要通過侵犯人體的免疫細(xì)胞,引起CD4+T淋巴細(xì)胞數(shù)量進(jìn)行性減少和多種免疫細(xì)胞量和質(zhì)的改變使得人體細(xì)胞免疫功能缺陷,導(dǎo)致艾滋病(acquired immure deficiency syndrome, AIDS)及各種機(jī)會感染、腫瘤的發(fā)生。高效抗反轉(zhuǎn)錄病毒治療(highly active antiretroviral therapy, HAART)能持續(xù)降低體內(nèi)HIV數(shù)量,重建免疫系統(tǒng),控制機(jī)會性感染、延緩病情進(jìn)展、減少疾病傳播,進(jìn)而提高患者的生活治療。NKG2D是一種C型凝集素樣活化型受體,具有高度保守性,主要表達(dá)于NK細(xì)胞、NKT細(xì)胞、CD8+T淋巴細(xì)胞、γδT細(xì)胞及某些狀態(tài)下的CD4+T淋巴細(xì)胞表面。近年來,NKG2D配體相繼被發(fā)現(xiàn),NKG2D配體具有驚人的多態(tài)性,且與MHCI分子差異性很大。本文將國內(nèi)首次研究NKG2D受體和配體表達(dá)及其在HIV-1感染中的臨床意義,HAART對NKG2D受體和配體表達(dá)的影響。 目的：研究外周血NK細(xì)胞表面NKG2D受體和CD4+T淋巴細(xì)胞表面NKG2D配體ULBP1、ULBP2的表達(dá)及其在HIV-1感染中的臨床意義；HAART對NKG2D受體和配體ULBP1、ULBP2表達(dá)的影響,進(jìn)一步探索艾滋病的發(fā)病機(jī)制及免疫重建機(jī)制。 方法：隨機(jī)選取16例健康志愿者(NC組)；未經(jīng)HAART的HIV-1組(HIV組)15例,未經(jīng)HAART的AIDS組(AIDS組)20例及經(jīng)嚴(yán)格的HAART1年組(HAART組)14例。密度梯度離心法從外周靜脈血中分離單個核細(xì)胞(PBMC),磁珠分選出NK細(xì)胞(CD56P日性細(xì)胞)和CD4+T淋巴細(xì)胞(CD3陽性CD4陽性細(xì)胞),流式細(xì)胞術(shù)檢測NK細(xì)胞表面NKG2D的表達(dá)水平,CD4+T淋巴細(xì)胞表面ULBP1、ULBP2配體的表達(dá)水平和ULBP1/ULBP2雙陽性細(xì)胞表達(dá)水平,同時檢測CD4+T淋巴細(xì)胞絕對計數(shù)與上述各項指標(biāo)的相關(guān)性。 結(jié)果：HIV感染后NK細(xì)胞表面NKG2D表達(dá)水平低于健康對照,隨著疾病的進(jìn)展,這種差異更明顯,高效抗逆轉(zhuǎn)錄病毒治療可以提高NKG2D表達(dá)。其中,HIV組低于NC組,AIDS組低于HIV組,]3AART組高于AIDS組。HIV感染后CD4+T淋巴細(xì)胞表面ULBP1、ULBP2表達(dá)水平上升,隨著疾病的進(jìn)展,這種上升更明顯,高效抗逆轉(zhuǎn)錄病毒治療可以逆轉(zhuǎn)這種上升。其中HIV組高于NC組,AIDS組高于HIV組,HAART組低于AIDS組。CD4+T淋巴細(xì)胞絕對數(shù)與NK細(xì)胞表面的NKG2D和CD4+T淋巴細(xì)胞表面ULBP1、ULBP2的表達(dá)存在相關(guān)關(guān)系。同時NKG2D與ULBP1、ULBP2存在相關(guān)關(guān)系。 結(jié)論：1.國內(nèi)首次觀察到HIV感染者外周血NK細(xì)胞表面NKG2D受體表達(dá)水平較正常人明顯降低,CD4+T淋巴細(xì)胞表面的NKG2D配體ULBP1和ULBP2表達(dá)較正常人明顯升高,三者的變化隨病情進(jìn)展(AIDS組)更顯著,且其變化與CD4+T淋巴細(xì)胞絕對計數(shù)存在相關(guān)關(guān)系；此外NK細(xì)胞表面NKG2D表達(dá)與CD4+T淋巴細(xì)胞表面ULBP1、ULBP2表達(dá)存在相關(guān)關(guān)系,提示NK細(xì)胞表面的NKG2D受體和CD4+T淋巴細(xì)胞表面的ULBP1、ULBP2均參與了HIV感染的免疫病理過程和免疫發(fā)病機(jī)制,且存在相互作用。2.首次觀察到HIV感染者尤其AIDS患者,外周血CD4+T淋巴細(xì)胞表面ULBP1/ULBP2雙陽性細(xì)胞表達(dá)較正常人升高,隨病情進(jìn)展其變化更顯著,且其表達(dá)與對應(yīng)的CD4+T淋巴細(xì)胞絕對計數(shù)及NK細(xì)胞表面NKG2D的表達(dá)存在相關(guān)關(guān)系。3.首次觀察到HIV感染者外周血NK細(xì)胞表面NKG2D受體水平、CD4+T淋巴細(xì)胞表面ULBP1和ULBP2配體水平及ULBP1/ULBP2雙陽性細(xì)胞表達(dá)水平的變化,經(jīng)過一年的HAART可以部分糾正這種變化,且與其對應(yīng)的CD4+T淋巴細(xì)胞絕對計數(shù)存在對應(yīng)關(guān)系,提示上述四者均可能參與了HIV感染者抗病毒治療的免疫重建過程。
[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.

【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R512.91

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