PROINFLAMMATORY CYTOKINES BLOCK T CELL DEATH IN VIVO

多年来，众所周知，将抗原注射到 动物导致携带CD4的T细胞活化和增殖， 细胞一旦激活的T细胞克隆性扩增到最大 水平，他们中的大多数继续通过凋亡死亡。此事件 这就提出了一个问题，即抗原引发的T细胞如何能够长期存活 足以发育成记忆细胞因此，这些T细胞中的许多必须是 能够抵抗死亡，否则一个记忆反应指向 抗原永远不会出现。最近，研究表明，T细胞 面对炎症反应时的克隆扩张阻止了 活化的T细胞死亡。因此，对抗原有反应的T细胞 将免于激活诱导的死亡。它 有人提出，活化的T细胞接受生存信号， 解除了死亡计划的管制例如，共注射 抗原与促炎细菌副产物， 脂多糖（LPS），导致T细胞的长期存活， 抗原应答细胞此外，LPS注射条件这些 细胞抵抗FAS死亡。T细胞存活的本质 信号未知。该项目的实验旨在 揭开这个信号的基础然而，已知LPS 不直接调节活化的T细胞，因此， 是与活化的T细胞相互作用的下游介质， 分离他们的死亡途径在这项研究中，我们将确定 脂多糖诱导的因子是拯救生命的关键 抗原激活的T细胞死亡。体内和体外 将进行实验以确定哪些细胞因子由 LPS对阻断死亡至关重要， 在被拯救的T细胞中失调。健康免疫系统的标志 是区分自身抗原和外来抗原的能力。所有人 通常发生对自身抗原的耐受性的破坏， 自身免疫性疾病。在许多情况下，自身免疫性与 炎症反应和炎症对适应性 对免疫性了解不多。这里描述的研究将导致 为了更好地理解炎症与 过程和T细胞存活。最终，这些研究可能会提供一个 更好地了解T细胞如何被激活以保护宿主免受 一种入侵的病原体，以及T细胞如何在免疫系统中失去自我耐受性。 并成为自体反应。

For many years it has been well known that injection of antigen into animals leads to the activation and proliferation of CD4 bearing T cells. Once the activated T cells have clonally expanded to a maximal level, the majority of them go on to die via apoptosis. This event raises the problem of how antigen-primed T cells ever survive long enough to develop into memory cells. Thus many of these T cells must be able to resist death otherwise a memory response directed towards the antigen would never occur. Recently, it has been shown that T cell clonal expansion in the face of an inflammatory response prevents the death of activated T cells. Therefore, T cells that respond to antigen at an inflammatory site will be spared from activation-induced death. It has been proposed that the activated T cells receive a survival signal which deregulates the death program. For example, co-injection of an antigen with the pro-inflammatory bacterial byproduct, lipopolysaccharide (LPS), leads to long-term T cell survival of the antigen responsive cells. Furthermore, LPS injection conditions these cells to resist FAS-based death. The nature of the T cell survival signal is unknown. The experiments in this project are designed to uncover the underpinnings of this signal. It is known, however, that LPS does not directly condition the activated T cell, therefore, there must be downstream mediators that interact with the activated T cells and uncouple their death pathways. In this study we will determine which factors induced by lipopolysaccharide are essential for rescuing antigen-activated T cells from death. Both in vivo and in vitro experiments will be conducted to determine which cytokines induced by LPS are essential to block death and which death pathways are deregulated in the rescued T cells. A hallmark of a health immune system is the ability to discern self antigen from foreign antigen. All to often a breakdown in tolerance to self antigen occurs which can lead to autoimmune disease. In many cases autoimmunity is associated with inflammatory responses and the effects of inflammation on adaptive immunity are not well understood. The studies described here will lead to a better understanding of the relationship between inflammatory processes and T cell survival. Ultimately these studies may provide a better understanding on how T cells are activated to protect a host from an invading pathogen and how T cells fail self tolerance in the periphery and become autoreactive.