CD4~+CD25~+T细胞在CD8~+T细胞抗肿瘤免疫中的调节作用

实验旨在研究CD4+CD25+T细胞在CD8+T细胞抗肿瘤免疫中的调节作用。将小鼠脾脏中分离的单个核细胞分为两组,即去除CD4+CD25+T细胞组和未去除CD4+CD25+T细胞组,测定树突状细胞提呈的肿瘤抗原多肽刺激不同T细胞增殖活性、细胞因子IFN-γ分泌,以及多肽特异性CD8+T细胞对同源性胃癌细胞株MFC的杀伤活性。结果显示预先去除未致敏T细胞中的CD4+CD25+T细胞,所诱导的特异性CD8+CTL对肿瘤细胞免疫应答增强,表现为反应性T细胞对树突状细胞提呈的肿瘤抗原多肽增殖反应增强,IFN-γ分泌量提高及CD8+T细胞对MFC杀伤活性增强。这些结果表明,预先去除未致敏T细胞中的CD4+CD25+T细胞,肿瘤抗原多肽修饰的树突状细胞肿瘤疫苗效能可明显增加。CD4+CD25+T细胞在CD8+T细胞抗肿瘤免疫中起下调作用。     

CD4+CD25+调节性T细胞与肿瘤免疫

CD4+CD25+调节性T细胞(CD4+CD25+Treg)是维持机体免疫耐受的一种重要因素。它组成性表达IL-2受体α链(CD25),主要的功能是抑制自身反应性T细胞的活化和功能,调节机体对抗原的免疫应答,从而使机体避免发生自身免疫病。近年来研究表明,Treg也可能通过相同的机制削弱机体的抗肿瘤效应。Treg介导的免疫抑制是肿瘤逃逸的原因之一。针对Treg进行肿瘤免疫治疗是一项可行的策略。     

CD4+CD25+调节性T细胞在肿瘤免疫中的作用

CD4+CD25+调节性T细胞(Tr)是体内自然发生的调节性T细胞的重要亚群,具有无反应性和免疫抑制两大特性,主要通过与靶细胞的直接接触而起作用,其在体内不仅参与自身免疫性疾病、移植排斥反应等,还在肿瘤的发生、发展及免疫治疗中发挥重要作用.近几年来,Tr在肿瘤免疫中的作用倍受关注.     

CD4+CD25+调节性T细胞参与肿瘤免疫逃逸的研究进展

CD4~+CD25~+调节性T细胞(regulatory T cells,Treg)是机体行使负性免疫调节的重要载体,在生理病理的诸多方面都有重要意义。本文旨就其与肿瘤的关联、介导逃逸的机制、细胞来源以及可能的临床运用作一综述。     

105 CD4+CD25+调节性T细胞和肿瘤免疫

近期研究发现一个有独特免疫调节功能的T细胞亚群CD4+CD25+调节性T细胞,不仅能抑制自身免疫性疾病发生,还可能参与肿瘤免疫的调节.这群细胞具有免疫无能和免疫抑制特性,通过与细胞直接接触发挥作用,而不依赖于其分泌的细胞因子.肿瘤环境中CD4+CD25+调节性T细胞比例增加,导致肿瘤免疫失调,去除这群细胞可有效诱导肿瘤免疫,为肿瘤治疗提供了一种新的方法.     

CD4~+CD25~+调节性T细胞和肿瘤免疫

近期研究发现一个有独特免疫调节功能的T细胞亚群 :CD4 + CD2 5 + 调节性T细胞 ,不仅能抑制自身免疫性疾病发生 ,还可能参与肿瘤免疫的调节。这群细胞具有免疫无能和免疫抑制特性 ,通过与细胞直接接触发挥作用 ,而不依赖于其分泌的细胞因子。肿瘤环境中CD4 + CD2 5 + 调节性T细胞比例增加 ,导致肿瘤免疫失调 ,去除这群细胞可有效诱导肿瘤免疫 ,为肿瘤治疗提供了一种新的方法。     

树突状细胞扩增抗原特异性CD4+ CD25+调节性T细胞研究进展

CD4+CD25+调节性T细胞(Tr)是同时具有免疫低反应性和免疫抑制性功能两大特征的T细胞.研究证实,CD4+ CD25+ Tr在抑制器官特异性自身免疫性疾病及GVHD是抗原特异性的,因此,应用器官特异性而不是多克隆性的Tr将大大促进以Tr为基础的免疫治疗.而具有调节活性的CD4+ CD25+ Tr仅占人类外周血CIM+ T细胞的1%～2%,因此,研究体外大量扩增的方法 对于以Tr基础的治疗至关重要.研究表明,树突状细胞(DC)作为机体强有力的专职抗原递呈细胞可以扩增具有抗原特异性的CD4+ CD25+ Tr且能增加后者的抑制活性,这为治疗自身免疫性疾病及GVHD提供了新的治疗前景.     

CD4+CD25+T细胞与移植免疫耐受

调节性T细胞是机体维持自身耐受的重要组成部分.CD4+CD25+T细胞以持续高表达CD25为特征,可通过细胞间直接接触或分泌TGF-β、IL-10来发挥抑制功能.它广泛参与自身免疫耐受、肿瘤免疫、移植免疫.现就其发育、特性、发挥功能的机制以及在移植免疫耐受中的作用和应用前景作一综述.     

CD4+ CD25+调节性T细胞在流产中的研究进展

CD4+CD25+调节性T细胞(Tr)是一个具有独特免疫调节功能的T细胞亚群.Tr免疫学特性主要在于抑制自身反应性T细胞的活化,并参与外周免疫耐受,对维持机体内环境的稳定起重要作用.Tr在流产中发挥重要的免疫调节作用.     

胃癌患者PBMCs中CD4+CD25+T细胞体外增殖及对CD4+CD25-T细胞增殖的影响

目的:探讨胃癌患者外周血单个核细胞（PBMCs）中的CD4+CD25+T细胞体外增殖及对CD4+CD25-T细胞增殖的影响。 方法:以免疫磁性分离方法 （MACS）分选出胃癌患者外周血单个核细胞中的CD4+CD25+T及CD4+CD25-T细胞后，用流式细胞仪分析细胞的纯度及活力；再以小鼠抗人CD3单抗、小鼠抗人CD28单抗及rh IL-2作为共刺激因子，观察与CD4+CD25-T细胞共培养时，CD4+CD25+T细胞对CD4+CD25-T细胞增殖的抑制效应。 结果:（1）分选后健康对照组及胃癌患者PBMC 中CD4+CD25+ T细胞纯度分别为83.8%±1.84%、84.13%±2.77％，两者相比，无显著差异（P＞0.05）;(2)经MACS 分选后正常对照组与胃癌患者CD4+CD25+ T细胞活力分别为98.52%±0.72%、97.80%±0.95%，两者相比，无显著差异（P＞0.05）；(3)无论是健康对照还是胃癌患者的CD4+CD25+T均具有明显抑制效应性T细胞如CD4+CD25-T细胞的增殖，随着CD4+CD25+T细胞数的增加，这种抑制增殖的能力也相应增加，当CD4+CD25+∶〖KG-*2〗CD4+CD25-T达 1∶〖KG-*2〗1时，抑制率最大达到50％。 结论:MACS分选法能够分选出高纯度及活力的CD4+CD25+T细胞，分选后CD4+CD25+T细胞在体外均能抑制CD4+CD25-T细胞增殖，且这种抑制效应呈一定效靶比关系。     

The role of self-peptides in the development of CD4+ CD25+ regulatory T cells

The thymus produces a unique lineage of cells known as CD4+ CD25+ regulatory T cells, and the exact processes leading to their development continue to be defined. Highly specific interactions between developing thymocytes and cognate self-antigens expressed by radioresistant elements in the thymus have been shown to drive CD4+ CD25+ regulatory-T-cell development. The self-peptide(s) that mediate thymic selection of CD4+ CD25+ regulatory T cells can also promote their expansion in the periphery, and self-peptides might also play a role in the conversion of CD4+ CD25- T cells into CD25+ regulatory T cells.     

CD25+ regulatory T cells and tumor immunity

Tumor cells express a range of antigens including self-antigens (those whose expression is shared by normal host tissue) and non-self antigens (such as those that arise as a result of mutations in normal cellular genes or in the case of some tumors, viral antigens). Immune responses to both types of antigen have been identified in human patients with cancer and in murine tumor models. In both cases, these responses are typically weak and generally fail to result in tumor rejection. Accumulating evidence indicates that a population of T cells, namely CD25(+) regulatory cells, is at least partly responsible for the poor immunogenicity of tumor cells. This evidence is discussed in the context of a murine model of melanoma.     

Human CD4+CD25+ regulatory T cells

In this report, we review studies of human CD4+CD25+ regulatory T cells (T-reg). Although lagging a few years behind the discovery of these cells in the mouse, the equivalent population of CD4+CD25+ regulatory T cells has also been isolated from human peripheral blood, thymus, lymph nodes and cord blood. In general, the characteristics of this T cell subset are strikingly similar between mouse and man. In the recent explosion of research reports on human CD4+CD25+ cells, although the majority of the characteristics ascribed to these cells appear to be consistent, contrasting results have been found primarily in regards to potential involvement of TGFbeta and production of IL-10. One explanation for this variability may reside in the fact that markedly different techniques are used to isolate human CD4+CD25+ T-reg cells and thus may result in the comparison of T-reg populations that differ in cellular composition and/or activation state. Another potential explanation for differences in human T-reg function may rest on the extreme variability of the culture conditions and TCR stimuli that have been used to test the functional properties of these cells in vitro. The strength of the TCR signal provided to the culture greatly affects the functional outcome of the co-culture and can result in the difference between suppression and full activation. Surprisingly, it appears that stronger stimulation has a greater and more rapid effect on the T-resp cell than on the T-reg cell as it causes T-resp cells to quickly become resistant to suppression. Thus, the details of in vitro culture conditions may at least partially account for disparate findings in regard to the functional characterization of human CD4+CD25+ cells. Here we review the evidence regarding the identification of human CD4+CD25+ regulatory T cells and their possible mechanism(s) of function.     

CD4+CD25+调节性T细胞在川崎病免疫发病机制中的作用

目的探讨CD4 CD25 调节性T细胞在川崎病(KD)免疫发病机制中的作用。方法急性期KD患儿25例,正常同年龄对照组25例,KD患儿分别于静脉丙种球蛋白(IVIG)治疗前后直接取血备检,未加任何体外丝裂原刺激培养。采用流式细胞术分别检测外周血CD4 CD25 调节性T细胞比例及CD14 细胞表面共刺激分子的表达;逆转录-聚合酶链反应(RT-PCR)及荧光定量PCR检测外周血CD4 T细胞中Foxp3、CTLA-4和GITR基因mRNA的表达。结果急性期KD患儿外周血CD4 CD25 调节性T细胞比例明显低于同年龄对照组(P<0.01),IVIG治疗后显著上升(P<0.01);急性期KD患儿外周血CD4 T细胞中Foxp3、CTLA-4和GITR基因mRNA表达水平均明显低于正常对照组(P<0.01),IVIG治疗后均有不同程度的恢复(P<0.01);急性期KD患儿CD14 细胞明显过度表达CD80及CD86等共刺激分子(P<0.01),IVIG治疗后CD80及CD86表达均显著下降。结论急性期KD患儿CD4 CD25 调节性T细胞数量减少可能与KD免疫调节功能紊乱有关。     

CD4+CD25+T调节细胞的研究进展

CD4 CD25 TH细胞通过抗原特异性方式或细胞接触的方式抑制自身反应性T细胞的活化,能有效地维持自身免疫耐受,是调节自身反应性T细胞和防止自身免疫病发生的重要调节细胞。