Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii.
Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii.
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DOI：
10.1371/journal.ppat.1000505
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发表时间：
2009-07
期刊：
影响因子：
6.7
通讯作者：
Hunter CA
中科院分区：
文献类型：
--
作者：
John B;Harris TH;Tait ED;Wilson EH;Gregg B;Ng LG;Mrass P;Roos DS;Dzierszinski F;Weninger W;Hunter CA
为了更好地了解感染过程中CD8 + T细胞应答的启动，使用双光子显微镜结合实验系统，允许树突状细胞（DC）和寄生虫特异性CD8 + T细胞的可视化，对细胞内寄生虫弓形虫的主要应答进行了表征。感染猫弓首蛔虫弓形虫诱导这两个群体定位于引流淋巴结的被膜下/滤泡间区域，并且DC是T细胞扩增所需的。与目前的模型一致，在同源抗原的存在下，CD8 + T细胞的平均速度降低。出乎意料的是，感染还导致非寄生虫特异性T细胞的行为的调节。这种TCR非依赖性过程与淋巴结微结构的重建以及CCL21和CCL3表达的变化相关。感染还导致DC和CD8 + T细胞之间的持续相互作用，其仅在同源抗原存在下可见，并且仅限于应答的早期阶段。在此时间范围内，淋巴结内感染的DC很少;然而，检测到呈递同源抗原的DC。总之，这些数据提供了新的见解DC和CD8 + T细胞之间的最早的相互作用，并表明，交叉呈递的旁观者DC，而不是感染的DC是一个重要的抗原呈递途径在弓形虫病。 弓形虫是一种原生动物寄生虫，可以感染包括人类在内的多种宿主。感染猫弓首蛔虫弓形虫对免疫功能低下的个体有潜在的生命威胁，并且在怀孕期间可能有害，经常导致胎儿流产。树突状细胞被认为通过其产生免疫信号（如细胞因子）以及加工和呈递寄生虫衍生肽至T细胞的能力在对弓形虫的保护性免疫的发展中起重要作用。然而，很少有人知道这些细胞类型之间的实际相互作用在一个完整的器官，如淋巴结，在感染过程中。使用双光子显微镜实时成像技术，我们已经确定了感染过程中树突状细胞和T细胞相互持续接触的非常早期的时间窗口，这对于产生保护性反应至关重要。我们还表明，由于感染，淋巴结微结构发生了重大变化，这反过来又可能对继发性病原体的免疫反应产生影响。了解体内这些免疫细胞之间的相互作用，导致对活性感染的抵抗，将有助于设计更好的策略，以在免疫功能低下的个体中产生针对这种病原体的保护性免疫反应。
To better understand the initiation of CD8+ T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8+ T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8+ T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8+ T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8+ T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis. Toxoplasma gondii is a protozoan parasite that can infect a wide range of hosts, including humans. Infection with T. gondii is potentially life threatening in immuno-compromised individuals and it can be detrimental during pregnancy, often leading to abortion of the fetus. Dendritic cells are thought to play a vital role in the development of protective immunity to Toxoplasma gondii through their ability to produce immunological signals such as cytokines and also process and present parasite derived peptides to T cells. However, little is known about the actual interactions between these cell types in an intact organ, such as the lymph node, during infection. Using the technology of live imaging by 2-photon microscopy we have identified a very early window of time during infection when dendritic cells and T cells make sustained contacts with one another, which appears crucial for the generation of protective responses. We also show that substantial changes are induced in the lymph node micro-architecture as a result of infection, which in turn could have effects on immune responses to secondary pathogens. Understanding the interaction between these immune cells in vivo that leads to resistance to active infection would help in the design of better strategies to develop protective immune responses against this pathogen in immuno-compromised individuals.
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