日本血吸虫感染对Th17细胞应答影响的研究
发布时间：2019-06-13 23:01
【摘要】：未致敏(na(l|¨)ve)CD~(4+)T细胞在外周淋巴组织中经病原体抗原刺激后,可分化成Th1和Th2两大类CD~(4+)效应T细胞。Th1细胞主要分泌IL-2、IFN-γ和TNF-β等细胞因子,调节细胞免疫;而Th2细胞主要分泌IL-4、IL-5、IL-6、IL-10及IL-13等细胞因子,调节体液免疫。同时,二者相互抑制、相互调节,协调参与维持机体的正常免疫功能。近年来,在一些自身免疫病和过敏原特异性反应研究中发现一种产生白介素17((interleukin17;IL--17))的特殊CD~(4+)T细胞。该型CD~(4+)T细胞同传统Th1和Th2细胞具有明显不同的特征。虽然其功能还没有被完全阐明,但越来越多的证据表明Th17细胞在宿主防御一些特定的胞外病原体、如不能被Th1类和Th2类有效清除的病原体起重要的保护作用。CD~(4+)T细胞除了分化为Th1、Th2和Th17这三大类效应细胞之外,还可以分化为一群CD~(4+)CD25+调节性T(Tregulatorycell,Treg)细胞,它主要通过细胞与细胞之间的直接接触和/或分泌一些抑制性细胞因子,如TGF-β和IL-10等发挥免疫负调控的作用;总之这些细胞亚群在清除感染、免疫病理损害中发挥着重要的作用。 与Th1和Th2细胞相似,Th17细胞的分化也需要特定的细胞因子和转录因子。TGF-β与IL--6的结合以及转录因子STAT3和RORγt对于Th117细胞的初始分化;IL---221对于Th117细胞的增殖;IL---223对于Th117细胞在外周的稳定均发挥重要的作用。与此相反,研究发现,Th1细胞及其分泌的IFN-γ和TTh2细胞及其分泌的IL--4能强烈地抑制Th117细胞的发育;与Treg细胞的功能密切相关的重要调节因子TGF-β在炎症因子IL--6不存在的情况下能够抑制Thl17细胞的分化,且Foxp3也可以通过下调IL-23等细胞因子的表达而抑制Th117细胞的分化。总之,这些Th17细胞的分化及调节因素一直是人们所关注的焦点,也已经成为近年来的研究热点。 日本血吸虫病作为一种典型的慢性感染性疾病的模型,能很好地诱导Th17细胞及Th1、Th2及Treg细胞的产生。尤其近年来,随着研究的深入,已有越来越多的文献报道,在血吸虫感染中Th17细胞参与了其后期的免疫病理反应-肝脏虫卵肉芽肿的形成。但是截至目前,关于这些细胞亚群之间、细胞因子之间以及细胞因子与细胞之间的相互影响、相互抑制的研究多数都是在较单一实验因素存在的情况、基于体外研究为主获得的结果。在一种复杂的感染过程中对于Th17细胞及其他CD4+T细胞亚群以及细胞因子之间的相互作用的动态变化研究还很少。 因此在本研究中,我们首先建立了日本血吸虫自然感染的小鼠模型,应用流式细胞仪,动态观察了感染不同阶段Th17细胞及其特征性细胞因子IL-17的水平、抑制Th17细胞的其它CD4+T细胞亚群、以及影响Th17细胞分化的相关细胞因子IFN-γ、IL-4、TGF-β、IL-6、IL-23、IL-21水平的变化并进行综合分析,从而探讨在复杂的感染过程中Th17细胞动态变化、以及其它CD4+T细胞亚群及细胞因子对Th17细胞可能的综合影响。随后,以血吸虫感染时最主要的两种粗分抗原SEA、SWA免疫小鼠,检测了SEA、SWA免疫后小鼠Th17细胞及其特征性细胞因子IL-17的水平、抑制Th17细胞的其它CD4+T细胞亚群、以及影响Th17细胞分化的相关细胞因子IFN-γ、IL-4、TGF-β、IL-6、IL-23、IL-21水平的变化并进行综合分析,以探讨SEA、SWA这两种粗分抗原分别对Th17细胞的诱导作用、以及同时诱导产生的其他影响Th17细胞的CD4+T细胞亚群及细胞因子对Th17细胞可能的综合影响。最后再给血吸虫感染小鼠体外注射rm-IL-17细胞因子和anti-IL-17中和抗体以使感染小鼠体内产生高水平和很低水平IL-17的状态,从而探讨Th17细胞及IL-17是否参与了宿主的抗血吸虫感染的保护性免疫应答。本研究获得如下主要结果: 1.在自然感染的过程中,当小鼠感染3周后,随着成虫开始产卵,肝脏的虫卵肉芽肿开始形成,并且伴随着肝脏虫卵肉芽肿的开始出现,Th17细胞占CD4+T细胞的百分比略有上升,在感染5周后开始显著上升,至感染8周时上升得最为明显,到感染13周时上升过程趋缓,即Th17细胞的比例随着感染的进展基本呈现上升的趋势;然而,同时Th1和Th2细胞的百分比也在上升,但是在感染的前3周Th1细胞增加的比例多于Th2细胞,相反,当成虫产卵后,Th2细胞的比例开始快速增长。同时,在感染慢性期Treg细胞的百分比明显上升。同时,细胞因子检测结果显示:促Th进17细胞的分化密切相关的细胞因子TGF-β、IL-6、IL-23和IL-21均随着感染时间的增加呈现一种基本上升的趋势,但同时抑制其分化的细胞因子IFN-γ和IL-4也是呈现稳定上升的趋势。以上所有结果均显示在日本血吸虫的自然感染过程中,全部都是由感染诱导的Th17细胞及促进其产生的细胞因子、与Th1、Th2和Treg细胞以及抑制Th17细胞产生的细胞因子呈现一种同步增长的趋势,提示我们这些抑制Th17细胞增长的因素在一种整体感染的情况下对Th17细胞的增长并没有发挥明显的抑制作用,进而提示我们在日本血吸虫感染后不同阶段的免疫应答状态都是由众多免疫效应相互影响、彼此叠加所形成的,即在感染的情况下,体内诱导因素和抑制因素同时存在,Th17细胞的增长可能是其诱导因素的作用强于抑制因素的结果。 2.采用SEA和SWA免疫小鼠后发现与PBS对照组相比,SEA优势诱导Th17细胞和Th2类应答以及参与免疫负调控的Treg细胞,SWA优势诱导Th1类应答。细胞因子检测结果显示与PBS对照组相比,在SEA组与Th17细胞的分化密切相关的细胞因子TGF-β、IL-6、IL-23和IL-21的水平均显著升高;而SWA组诱导产生的细胞因子TGF-β和IL-6的水平也显著升高,IL-23和IL-21的水平仅轻度升高。同时,考虑到抑制Th17细胞的Th1、Th2、Treg细胞及抑制性细胞因子的表达水平虽然在SWA和SEA免疫后明显升高,但考虑到抗原免疫后Th17细胞同时增多,因而推测在Th17细胞的分化中这些抑制性细胞因子可能并没有发挥主导作用。 3.将小鼠腹腔注射rm-IL-17细胞因子(以模拟体内高于正常浓度IL-17的状态)及对照PBS、或注射anti-IL-17中和抗体(以模拟体内低于正常浓度IL-17的状态)及同型对照抗体。结果显示,增高或降低小鼠体内IL-17浓度都能或多或少的影响抗体应答水平,但不能有效地增强(或抑制)与宿主抗血吸虫感染高保护力密切相关的Th细胞应答,而Treg细胞的比例却明显减少。根据我们现有的实验证据,无法给予明确的提示来说明这些抗体及细胞水平的改变可能会对免疫保护力产生何种影响。虽然我们观察到促进与抑制Th17细胞分化的细胞因子水平大多显著升高,但对Th17细胞本身的数量却未见明显的影响。然而,降低小鼠体I内L-17浓度似乎对宿主抗血吸虫感染的保护性免疫力有一定的提高,但根据我们目前的研究数据,尚无法阐明其原因。 综上所述,本研究中我们发现,在自然感染过程中,Th17细胞与Th1、Th2和Treg细胞一起呈现一种同步增长的趋势,提示我们Th1、Th2和Treg细胞这些在体外或单一(简单)实验因素中已被广泛证明可显著抑制Th17细胞增长的因素在复杂的体内感染情况下,对Th17细胞的增长并没有发挥主导性的抑制作用。在粗分抗原中,我们发现SEA能够优势诱导Th17细胞的产生(P0.05)。此外,我们还发现在日本血吸虫感染过程中,Th17细胞及其分泌的细胞因子IL-17对宿主抗血吸虫感染的免疫保护力的影响不明显。总之,在一种具体而复杂的病原体感染过程中,细胞亚群之间、细胞因子之间、细胞与细胞因子之间的相互影响、相互抑制作用以及其他因子协调作用共同组成复杂的调节网络调控Th17细胞分化。
[Abstract]:Non-sensitized (na (l | 1)-ve) CD ~ (4 +) T-cells can differentiate into two types of CD ~ (4 +)-effector T cells in peripheral lymphoid tissue. Th1 cells mainly secrete cytokines such as IL-2, IFN-2 and TNF-1, regulate cellular immunity, and Th2 cells mainly secrete cytokines such as IL-4, IL-5, IL-6, IL-10 and IL-13, and regulate humoral immunity. At the same time, the two are mutually inhibited, mutually adjusted, and the normal immune function of the machine body is coordinated. In recent years, a special CD ~ (4 +) T cell producing interleukin17 (IL-17) was found in some autoimmunity and allergen-specific response studies. The CD ~ (4 +) T cells have distinct characteristics with the traditional Th1 and Th2 cells. Although its function is not fully set out, more and more evidence suggests that Th17 cells play an important protective role in the host defense of some specific extracellular pathogens, such as pathogens that cannot be effectively removed by the Th1 and Th2 classes. The CD ~ (4 +) T cells can also be differentiated into a group of CD ~ (4 +) CD25 + regulatory T (Tregs, Treg) cells in addition to the three types of effector cells that are differentiated into Th1, Th2 and Th17, which mainly contact and/ or secrete some inhibitory cytokines by direct contact between the cells and the cells, Such as TGF-1 and IL-10, which play an important role in the elimination of infection and immunopathological damage. Similar to Th1 and Th2 cells, the differentiation of Th17 cells also requires specific cytokines and transcription factors The combination of TGF-1 with IL-6 and the initial differentiation of transcription factors STAT3 and STAT3 on the Th117 cells; the proliferation of IL--221 for Th117 cells; and IL--223 play an important role in the stability of Th117 cells in the periphery In contrast, the study found that Th1 cells and their secreted IFN-1 and TTh2 cells and their secreted IL-4 can strongly inhibit the development of Th117 cells, and the important regulatory factors, TGF-1, which are closely related to the function of Treg cells, can inhibit the distribution of Th17 cells in the absence of inflammatory factor IL-6. Foxp3 can also inhibit the distribution of Th117 cells by down-regulating the expression of cytokines such as IL-23. In conclusion, the differentiation and regulation factors of these Th17 cells have been the focus of attention, and have become the research heat in recent years. Point. Schistosomiasis japonica is a model of a typical chronic infectious disease, which can induce Th17 cells and Th1, Th2 and Treg cells well. In recent years, more and more literature has been reported in recent years. Th17 cells in the infection of Schistosoma japonicum have been involved in the later-stage immune-pathological reaction-liver egg granuloma. However, as of the present, studies on the interaction between these cell subpopulations, between cytokines, and between the cytokines and the cells, are mostly in the presence of a single experimental factor and are based on in vitro studies The dynamic changes of the interaction between Th17 cells and other CD4 + T cell subpopulations and cytokines in a complex infection process In this study, we first established a mouse model of the natural infection of Schistosoma japonicum, and the flow cytometry was applied to observe the level of Th17 cells and its characteristic cytokines IL-17 in different stages of infection and to inhibit the other CD4 + of Th17 cells. The changes of T-cell subpopulations and related cytokines, IFN-1, IL-4, TGF-1, IL-6, IL-23, and IL-21, which affect the differentiation of Th17 cells, and the comprehensive analysis were carried out, and the Th17 fine in complex infection was discussed. Cell dynamics, as well as other CD4 + T cell subpopulations and cytokine-to-Th17 cells The effects of SEA and SWA on the level of Th17 cells and their characteristic cytokines, IL-17, the other CD4 + T cell subpopulations of Th17 cells, and the related cytokines that affect the differentiation of Th17 cells were detected. The changes of the levels of IFN-1, IL-4, TGF-1, IL-6, IL-23, and IL-21 and the comprehensive analysis were carried out to study the induced effects of SEA and SWA on the induction of Th17 cells. And finally, the mice infected with the schistosome infected mice were injected with a rm-IL-17 cytokine and an anti-IL-17 to produce a high level and a low level of IL-17 in the infected mice, so as to explore whether the Th17 cells and the IL-17 are involved in the protection of the anti-schistosome infection of the host. sexual immune response. This study was obtained, for example, The main results were as follows:1. In the course of natural infection, when the mice were infected for 3 weeks, the egg granuloma of the liver began to form as the adults began to lay eggs, and the Th17 cells occupied the CD4 + T cells with the onset of the granuloma of the egg of the liver. The percentage of Th1 and Th2 cells increased significantly after 5 weeks of infection, most notably at 8 weeks of infection, and the increase in the increase in the rise in the 13-week period of infection, that is, the proportion of Th17 cells increased substantially with the progression of infection; however, both Th1 and Th2 cells The percentage is also rising, but the ratio of Th1 cells to increase in the first 3 weeks of the infection is more than that of the Th2 cells, in contrast, the ratio of the Th2 cells when the adult lays eggs The case began to grow rapidly. At the same time, Treg cells were infected at the same time. The results showed that the cytokines, TGF-1, IL-6, IL-23, and IL-21, which were closely related to the differentiation of Th in 17 cells, showed an increase in the time of infection. The tendency to rise substantially, but at the same time, the cytokine, IFN-1, and IL-4, which inhibit its differentiation, are also present. All of the above results are shown in the course of the natural infection of the Schistosoma japonicum, all of the Th17 cells induced by infection and the cytokines that promote their production, and the presence of one of Th1, Th2 and Treg cells as well as the cytokines that inhibit the production of Th17 cells. The trend of synchronous growth indicates that the factors that inhibit the growth of Th17 cells in the case of a whole infection do not have a significant inhibition effect on the growth of Th17 cells, thus suggesting that the immune response state of the different stages after the infection of the Schistosoma japonicum is a large number of immune responses. In the case of infection, the effect of the growth of Th17 cells is stronger than that of the induction factor. Results of the inhibition factor.2. After using SEA and SWA to immunize the mice, it was found that the SEA advantage induced the Th17 cells and the Th2 response as well as the Treg cells that were involved in the negative regulation of the immune response, and the SWA was excellent. There was a significant increase in the levels of the cytokines TGF-1, IL-6, IL-23 and IL-21, which were closely related to the differentiation of the group of SEA and Th17 cells compared with the PBS control group, and the cytokine TGF-1 and IL-21 induced by the SWA group. The levels of IL-23 and IL-2 were also significantly elevated The levels of Th1, Th2, Treg cells and inhibitory cytokines, which inhibit the Th17 cells, were only slightly increased, while the level of expression of Th1, Th2, Treg cells, and inhibitory cytokines, which inhibited the Th17 cells, increased significantly after the immunization of SWA and SEA, but taking into account T h17 cells increase at the same time, and it is presumed that these inhibitory cytokines may be present in the differentiation of Th17 cells 3. Mouse peritoneal injection of rm-IL-17 cytokine (to mimic the state of IL-17 above normal in vivo) and control PBS, or injection of anti-IL-17 neutralizing antibody (to mimic normal concentration of IL-17 in vivo) The results showed that the increase or decrease of the IL-17 concentration in the mice can more or less influence the antibody response level, but it is not effective to enhance (or inhibit) the Th cell response which is closely related to the high protective force of the host anti-schistosome infection, and the Tre The proportion of g cells is obviously reduced. According to our existing experimental evidence, it is not possible to give clear tips to indicate that changes in these antibodies and cell levels may be In spite of the significant increase in the level of cytokines that promote and inhibit the differentiation of Th17 cells, we have observed that the Th17 cells themselves However, decreasing the L-17 concentration in the body of the mouse seems to have a certain increase in the protective immunity of the host against the schistosome infection, but according to our present study In conclusion, we have found that Th17 cells, together with Th1, Th2 and Treg cells, present a synchronization in the course of natural infection. The trend of growth suggests that these factors, Th1, Th2 and Treg cells, have been widely demonstrated in in vitro or single (simple) experimental factors to significantly inhibit the growth of Th17 cells in complex in-vivo infections, with the growth of Th17 cells We found that SEA can lead to the differentiation of Th1/ Th2 cells. In addition, we found that in the course of the infection of Schistosoma japonicum, Th17 cells and their secreted cytokines IL-17 were sensitive to the host anti-schistosome. The effect of the immune protective force of the dye is not obvious. In conclusion, in a specific and complex pathogen infection process, the interaction between the cell subsets, the cytokines, the interaction between the cells and the cytokines, the mutual inhibition and the coordination of other factors together form a complex modulation.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392
本文编号：2498885
[Abstract]:Non-sensitized (na (l | 1)-ve) CD ~ (4 +) T-cells can differentiate into two types of CD ~ (4 +)-effector T cells in peripheral lymphoid tissue. Th1 cells mainly secrete cytokines such as IL-2, IFN-2 and TNF-1, regulate cellular immunity, and Th2 cells mainly secrete cytokines such as IL-4, IL-5, IL-6, IL-10 and IL-13, and regulate humoral immunity. At the same time, the two are mutually inhibited, mutually adjusted, and the normal immune function of the machine body is coordinated. In recent years, a special CD ~ (4 +) T cell producing interleukin17 (IL-17) was found in some autoimmunity and allergen-specific response studies. The CD ~ (4 +) T cells have distinct characteristics with the traditional Th1 and Th2 cells. Although its function is not fully set out, more and more evidence suggests that Th17 cells play an important protective role in the host defense of some specific extracellular pathogens, such as pathogens that cannot be effectively removed by the Th1 and Th2 classes. The CD ~ (4 +) T cells can also be differentiated into a group of CD ~ (4 +) CD25 + regulatory T (Tregs, Treg) cells in addition to the three types of effector cells that are differentiated into Th1, Th2 and Th17, which mainly contact and/ or secrete some inhibitory cytokines by direct contact between the cells and the cells, Such as TGF-1 and IL-10, which play an important role in the elimination of infection and immunopathological damage. Similar to Th1 and Th2 cells, the differentiation of Th17 cells also requires specific cytokines and transcription factors The combination of TGF-1 with IL-6 and the initial differentiation of transcription factors STAT3 and STAT3 on the Th117 cells; the proliferation of IL--221 for Th117 cells; and IL--223 play an important role in the stability of Th117 cells in the periphery In contrast, the study found that Th1 cells and their secreted IFN-1 and TTh2 cells and their secreted IL-4 can strongly inhibit the development of Th117 cells, and the important regulatory factors, TGF-1, which are closely related to the function of Treg cells, can inhibit the distribution of Th17 cells in the absence of inflammatory factor IL-6. Foxp3 can also inhibit the distribution of Th117 cells by down-regulating the expression of cytokines such as IL-23. In conclusion, the differentiation and regulation factors of these Th17 cells have been the focus of attention, and have become the research heat in recent years. Point. Schistosomiasis japonica is a model of a typical chronic infectious disease, which can induce Th17 cells and Th1, Th2 and Treg cells well. In recent years, more and more literature has been reported in recent years. Th17 cells in the infection of Schistosoma japonicum have been involved in the later-stage immune-pathological reaction-liver egg granuloma. However, as of the present, studies on the interaction between these cell subpopulations, between cytokines, and between the cytokines and the cells, are mostly in the presence of a single experimental factor and are based on in vitro studies The dynamic changes of the interaction between Th17 cells and other CD4 + T cell subpopulations and cytokines in a complex infection process In this study, we first established a mouse model of the natural infection of Schistosoma japonicum, and the flow cytometry was applied to observe the level of Th17 cells and its characteristic cytokines IL-17 in different stages of infection and to inhibit the other CD4 + of Th17 cells. The changes of T-cell subpopulations and related cytokines, IFN-1, IL-4, TGF-1, IL-6, IL-23, and IL-21, which affect the differentiation of Th17 cells, and the comprehensive analysis were carried out, and the Th17 fine in complex infection was discussed. Cell dynamics, as well as other CD4 + T cell subpopulations and cytokine-to-Th17 cells The effects of SEA and SWA on the level of Th17 cells and their characteristic cytokines, IL-17, the other CD4 + T cell subpopulations of Th17 cells, and the related cytokines that affect the differentiation of Th17 cells were detected. The changes of the levels of IFN-1, IL-4, TGF-1, IL-6, IL-23, and IL-21 and the comprehensive analysis were carried out to study the induced effects of SEA and SWA on the induction of Th17 cells. And finally, the mice infected with the schistosome infected mice were injected with a rm-IL-17 cytokine and an anti-IL-17 to produce a high level and a low level of IL-17 in the infected mice, so as to explore whether the Th17 cells and the IL-17 are involved in the protection of the anti-schistosome infection of the host. sexual immune response. This study was obtained, for example, The main results were as follows:1. In the course of natural infection, when the mice were infected for 3 weeks, the egg granuloma of the liver began to form as the adults began to lay eggs, and the Th17 cells occupied the CD4 + T cells with the onset of the granuloma of the egg of the liver. The percentage of Th1 and Th2 cells increased significantly after 5 weeks of infection, most notably at 8 weeks of infection, and the increase in the increase in the rise in the 13-week period of infection, that is, the proportion of Th17 cells increased substantially with the progression of infection; however, both Th1 and Th2 cells The percentage is also rising, but the ratio of Th1 cells to increase in the first 3 weeks of the infection is more than that of the Th2 cells, in contrast, the ratio of the Th2 cells when the adult lays eggs The case began to grow rapidly. At the same time, Treg cells were infected at the same time. The results showed that the cytokines, TGF-1, IL-6, IL-23, and IL-21, which were closely related to the differentiation of Th in 17 cells, showed an increase in the time of infection. The tendency to rise substantially, but at the same time, the cytokine, IFN-1, and IL-4, which inhibit its differentiation, are also present. All of the above results are shown in the course of the natural infection of the Schistosoma japonicum, all of the Th17 cells induced by infection and the cytokines that promote their production, and the presence of one of Th1, Th2 and Treg cells as well as the cytokines that inhibit the production of Th17 cells. The trend of synchronous growth indicates that the factors that inhibit the growth of Th17 cells in the case of a whole infection do not have a significant inhibition effect on the growth of Th17 cells, thus suggesting that the immune response state of the different stages after the infection of the Schistosoma japonicum is a large number of immune responses. In the case of infection, the effect of the growth of Th17 cells is stronger than that of the induction factor. Results of the inhibition factor.2. After using SEA and SWA to immunize the mice, it was found that the SEA advantage induced the Th17 cells and the Th2 response as well as the Treg cells that were involved in the negative regulation of the immune response, and the SWA was excellent. There was a significant increase in the levels of the cytokines TGF-1, IL-6, IL-23 and IL-21, which were closely related to the differentiation of the group of SEA and Th17 cells compared with the PBS control group, and the cytokine TGF-1 and IL-21 induced by the SWA group. The levels of IL-23 and IL-2 were also significantly elevated The levels of Th1, Th2, Treg cells and inhibitory cytokines, which inhibit the Th17 cells, were only slightly increased, while the level of expression of Th1, Th2, Treg cells, and inhibitory cytokines, which inhibited the Th17 cells, increased significantly after the immunization of SWA and SEA, but taking into account T h17 cells increase at the same time, and it is presumed that these inhibitory cytokines may be present in the differentiation of Th17 cells 3. Mouse peritoneal injection of rm-IL-17 cytokine (to mimic the state of IL-17 above normal in vivo) and control PBS, or injection of anti-IL-17 neutralizing antibody (to mimic normal concentration of IL-17 in vivo) The results showed that the increase or decrease of the IL-17 concentration in the mice can more or less influence the antibody response level, but it is not effective to enhance (or inhibit) the Th cell response which is closely related to the high protective force of the host anti-schistosome infection, and the Tre The proportion of g cells is obviously reduced. According to our existing experimental evidence, it is not possible to give clear tips to indicate that changes in these antibodies and cell levels may be In spite of the significant increase in the level of cytokines that promote and inhibit the differentiation of Th17 cells, we have observed that the Th17 cells themselves However, decreasing the L-17 concentration in the body of the mouse seems to have a certain increase in the protective immunity of the host against the schistosome infection, but according to our present study In conclusion, we have found that Th17 cells, together with Th1, Th2 and Treg cells, present a synchronization in the course of natural infection. The trend of growth suggests that these factors, Th1, Th2 and Treg cells, have been widely demonstrated in in vitro or single (simple) experimental factors to significantly inhibit the growth of Th17 cells in complex in-vivo infections, with the growth of Th17 cells We found that SEA can lead to the differentiation of Th1/ Th2 cells. In addition, we found that in the course of the infection of Schistosoma japonicum, Th17 cells and their secreted cytokines IL-17 were sensitive to the host anti-schistosome. The effect of the immune protective force of the dye is not obvious. In conclusion, in a specific and complex pathogen infection process, the interaction between the cell subsets, the cytokines, the interaction between the cells and the cytokines, the mutual inhibition and the coordination of other factors together form a complex modulation.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392
【参考文献】
相关期刊论文 前2条
1 刘光伟;赵勇;;CD4~+T细胞的新亚型:Th17细胞及其生物效应[J];生物化学与生物物理进展;2007年04期
2 吴长有;;Th17细胞:一种新的效应CD4~+T细胞亚群[J];细胞与分子免疫学杂志;2006年06期
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