本文選題：胸腺　切入點(diǎn)：異種移植　出處：《第三軍醫(yī)大學(xué)》2005年博士論文

【摘要】： 背景及目的:胸腺是培訓(xùn)胸腺細(xì)胞發(fā)育的首要場(chǎng)所,來源于骨髓的前T細(xì)胞進(jìn)入胸腺環(huán)境中,從胸腺被膜下區(qū),經(jīng)胸腺皮質(zhì)向皮質(zhì)皮髓交界區(qū)、髓質(zhì)移動(dòng),經(jīng)一系列復(fù)雜的培訓(xùn)過程,包括增殖、受體基因重排、MHC限制的陽性選擇、排除自身反應(yīng)性和缺陷細(xì)胞的陰性選擇、細(xì)胞表面分子和功能上的成熟等,確保了外周成熟T細(xì)胞可識(shí)別外源性抗原肽和自身MHC復(fù)合物(自身MHC限制性),并消除自身反應(yīng)性T細(xì)胞(自身耐受)。這個(gè)過程中每一步都是在胸腺的微環(huán)境中進(jìn)行,胸腺微環(huán)境主要由胸腺基質(zhì)細(xì)胞和細(xì)胞外基質(zhì)組成,其中胸腺基質(zhì)細(xì)胞是胸腺微環(huán)境中最重要的成分。胸腺基質(zhì)細(xì)胞在胸腺中以三維立體構(gòu)成網(wǎng)狀支架結(jié)構(gòu),胸腺細(xì)胞與基質(zhì)細(xì)胞在不同區(qū)域的相互作用對(duì)精密有序地完成了陽性選擇和陰性選擇起重要的作用。胸腺基質(zhì)細(xì)胞在空間、時(shí)間上為胸腺細(xì)胞的培訓(xùn)提供了最適合的微環(huán)境,對(duì)胸腺細(xì)胞分化以及功能性亞群的形成有決定性的作用。 胸腺不僅在建立和塑造有功能的T細(xì)胞庫中發(fā)揮作用,而且對(duì)誘導(dǎo)和維持自身耐受和移植耐受起關(guān)鍵作用。經(jīng)胸腺途徑誘導(dǎo)免疫耐受已進(jìn)行了廣泛研究,主要的機(jī)理是通過胸腺的選擇作用,消除自身、同種、異種供體反應(yīng)性T細(xì)胞,從而達(dá)到較穩(wěn)定的免疫耐受。最近發(fā)現(xiàn)在胸腺基質(zhì)細(xì)胞廣泛地表達(dá)外周組織器官的組織特異性抗原,所以胸腺基質(zhì)細(xì)胞被認(rèn)為是外周組織器官的自身抗原庫的鏡子,在自身耐受和維持免疫自身穩(wěn)定起著關(guān)鍵性作用。異種胸腺移植不僅可以重建有功能的細(xì)胞免疫功能,而且可以誘導(dǎo)供者特異性免疫耐受,但其面臨的主要問題是宿主T細(xì)胞在異種胸腺內(nèi)成熟后不能產(chǎn)生對(duì)宿主抗原足夠的自身耐受,而發(fā)生了多器官的自身免疫損害,如甲狀腺炎、淚腺炎、卵巢炎以及胃炎等,而同系或同種胸腺移植的受者未發(fā)生自身免疫綜合征。我們以前將同系胸腺與異種胸腺充分混合后再進(jìn)行移植,既能誘導(dǎo)供體特異性的免疫耐受,又能防止自身免疫損害的發(fā)生。然而胸腺細(xì)胞在混合胸腺中是如何被訓(xùn)練的并不清楚;也不知道從骨髓來源的前T細(xì)胞進(jìn)入混合胸腺后,是一個(gè)克隆的T細(xì)胞經(jīng)歷混合胸腺中的一個(gè)胸腺培訓(xùn),還是要經(jīng)歷兩個(gè)不同胸腺的共同培訓(xùn)?因此我們?cè)O(shè)計(jì)了將不同種類的兩種胸腺分別移植在一個(gè)機(jī)體內(nèi)的不同部位,并進(jìn)行T細(xì)胞示蹤
[Abstract]:Background and objective: the thymus is the primary place for training thymocytes to develop. The former T cells from bone marrow enter the thymus environment and move from the thymic submembrane region, the thymic cortex to the cortical medullary junction region, and the medulla. After a series of complex training processes, including proliferation, receptor gene rearrangement, MHC restricted positive selection, exclusion of self-reactivity and negative selection of defective cells, cell surface molecular and functional maturation, etc. It ensures that peripheral mature T cells can recognize exogenous antigenic peptides and their own MHC complexes (self MHC restricted T cells) and eliminate autoreactive T cells (autotolerance). Each step of this process takes place in the microenvironment of the thymus. Thymic microenvironment is mainly composed of thymic stromal cells and extracellular matrix, among which thymic stromal cells are the most important components in thymus microenvironment. The interaction between thymocytes and stromal cells in different regions plays an important role in the precise and orderly completion of positive and negative selection. Thymic stromal cells provide the most suitable microenvironment for the training of thymocytes in space and time. It plays a decisive role in the differentiation of thymocytes and the formation of functional subsets. Thymus not only plays a role in the establishment and formation of functional T cell banks, but also plays a key role in inducing and maintaining self-tolerance and transplantation tolerance. The induction of immune tolerance through thymus pathway has been extensively studied. The main mechanism is to eliminate self, allogeneic and xenogeneic donor reactive T cells through thymus selection. It has recently been found that thymic stromal cells widely express tissue-specific antigens in peripheral tissues and organs, so thymic stromal cells are considered to be a mirror of the antigen-library of peripheral tissues and organs. Xenogeneic thymus transplantation can not only reconstruct the functional cellular immune function, but also induce donor specific immune tolerance. However, the main problem it faces is that the host T cells cannot produce sufficient tolerance to host antigens after maturation in the xenogeneic thymus, and autoimmune damage occurs in many organs, such as thyroiditis, lacrimal gland inflammation, ovary inflammation and gastritis, etc. But the recipient of homologous or allogeneic thymus transplantation did not develop autoimmune syndrome. We used to mix homologous thymus with heterologous thymus before transplantation, which can induce donor-specific immune tolerance. But it's not clear how the thymocytes are trained in the mixed thymus, or how they get into the mixed thymus from pre-T cells from bone marrow. Is a cloned T cell trained in a single thymus in a mixed thymus, or is it a common training for two different thymus? So we designed to transplant two different kinds of thymus into different parts of the body and do T cell tracing.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R392

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 解志杰,吳軍,鄭峻松,彭雙發(fā),易紹萱,陳希煒;混合胸腺裸小鼠移植模型的建立及重建T細(xì)胞功能的體外研究[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2004年03期

2 解志杰,吳軍,鄭峻松,彭雙發(fā);混合胸腺移植誘導(dǎo)皮膚移植物免疫耐受的實(shí)驗(yàn)研究[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2004年23期

3 解志杰,吳軍;異種移植中的排斥反應(yīng)及其對(duì)策研究進(jìn)展[J];中華燒傷雜志;2003年05期

相關(guān)博士學(xué)位論文 前1條

1 解志杰;混合胸腺移植誘導(dǎo)移植耐受及預(yù)防自身免疫損害的研究[D];第三軍醫(yī)大學(xué);2003年

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