【摘要】：免疫記憶是免疫系統(tǒng)的一大特征,少量的記憶性細(xì)胞便能對(duì)再次免疫應(yīng)答產(chǎn)生顯著的影響,但其發(fā)揮作用的機(jī)制并不十分清楚。樹突狀細(xì)胞(DCs)是專職性抗原提呈細(xì)胞,DC的功能狀態(tài)以及不同的DC亞群對(duì)特異性免疫細(xì)胞的分化方向和反應(yīng)強(qiáng)度起到?jīng)Q定性的作用,在激發(fā)免疫應(yīng)答和誘導(dǎo)免疫耐受中均發(fā)揮著關(guān)鍵作用。目前發(fā)現(xiàn),DC對(duì)于不同的T細(xì)胞亞群包括免疫記憶性T細(xì)胞的形成具有重要作用。記憶性CD4T細(xì)胞由于其數(shù)量稀少難以獲得,所以對(duì)于記憶性CD4T細(xì)胞與其它免疫細(xì)胞亞群的相互作用的研究比較少,其中,記憶性CD4T細(xì)胞對(duì)DC具體功能的調(diào)控和機(jī)制仍不完全清楚。 我們?cè)谇捌谘芯恐邪l(fā)現(xiàn)調(diào)節(jié)性DC可誘導(dǎo)產(chǎn)生一群高分泌IL-4/IL-10的記憶性Th2細(xì)胞(命名為Tm2),Tm2可通過IL-10抑制成熟DC誘導(dǎo)的CD4T細(xì)胞增殖；同時(shí)建立了能夠大量制備該記憶性細(xì)胞亞群的體外培養(yǎng)體系以便于開展功能研究。在本研究中,我們深入研究了Tm2對(duì)DC功能的直接調(diào)控作用及其相關(guān)機(jī)制。我們發(fā)現(xiàn),Tm2能夠抑制DC表面共刺激分子CD80和CD86的表達(dá),抑制其IL-6、IL-1β和IL-12p70的表達(dá),使得DC促進(jìn)初始T細(xì)胞增殖和活化的能力下降。Tm2對(duì)DC的這種效應(yīng)依賴于抗原特異性的活化,并且依賴于活化后IL-10和IL-4的分泌。而且在體內(nèi),Tm2也能抑制免疫狀態(tài)下淋巴結(jié)中DC表面CD86的表達(dá)。本研究結(jié)果提示,記憶性CD4T細(xì)胞可以通過改變DC的功能狀態(tài),發(fā)揮并且放大其免疫抑制效應(yīng),參與調(diào)控再次免疫應(yīng)答的效應(yīng)。本研究進(jìn)一步深化了對(duì)記憶性T細(xì)胞發(fā)揮作用機(jī)制的認(rèn)識(shí),并深入認(rèn)識(shí)DC在再次免疫應(yīng)答中受到記憶性CD4T細(xì)胞亞群的精細(xì)調(diào)控,為疫苗的設(shè)計(jì)和應(yīng)用提供了理論基礎(chǔ)。
[Abstract]:Immune memory is a major feature of the immune system, a small number of memory cells can have a significant impact on the re-immune response, but the mechanism of its role is not very clear. Dendritic cells (DCs) are specialized antigen presenting cells. The functional status of DC and different DC subsets play a decisive role in the differentiation direction and response intensity of specific immune cells. It plays a key role in stimulating immune response and inducing immune tolerance. It has been found that DC plays an important role in the formation of different T cell subsets, including immune memory T cells. Because the number of memory CD4T cells is scarce and difficult to obtain, the interaction between memory CD4T cells and other immune cell subsets is less studied. Among them, the regulation and mechanism of memory CD4T cells on the specific function of DC are still unclear. In previous studies, we found that regulatory DC could induce the production of a group of memory Th2 cells (named Tm2) with high secretion of IL-4/IL-10, and Tm2 could inhibit the proliferation of CD4T cells induced by mature DC through IL-10. At the same time, an in vitro culture system was established to prepare the memory cell subsets in large quantities for the purpose of functional study. In this study, we studied the direct regulation of DC function by Tm2 and its related mechanisms. We found that Tm2 could inhibit the expression of CD80 and CD86, IL-6,IL-1 尾 and IL-12p70 on the surface of DC. The ability of DC to promote the proliferation and activation of primary T cells was decreased. This effect of Tm2 on DC was dependent on antigen-specific activation and on the secretion of IL-10 and IL-4 after activation. In vivo, Tm2 can also inhibit the expression of CD86 on DC surface in immune lymph nodes. Our results suggest that memory CD4T cells can play and amplify the immunosuppressive effect of DC by changing the functional state of DC, and participate in the regulation of reimmune response. This study has further deepened the understanding of the mechanism of memory T cells and the fine regulation of DC by memory CD4T cell subsets in the reimmune response, which provides a theoretical basis for the design and application of vaccines.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R392

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本文編號(hào)：2392754