Regulation of the function of CD4 T cells

我们的研究旨在回答两个关于免疫反应如何调节的基本问题：当抗原冲击免疫系统时，是什么决定了抗原（外来或自身）是否启动免疫反应？第二，如果免疫反应启动，是什么决定了免疫反应的类型，其中有两种主要类型？例如，免疫系统可以产生由“细胞毒性T细胞”组成的细胞介导的应答，其可以杀死肿瘤细胞或被病毒感染的细胞，和/或其可以产生抗体，所述抗体例如中和一些病原性细菌产生的毒素。值得注意的是，免疫系统有一种方法来决定产生哪种类型的反应：主要的细胞介导的反应，主要的抗体反应或混合反应。这种“决定”通常是至关重要的，因为不同种类的免疫力对不同的入侵者有效。已经清楚的是，免疫系统的细胞，“CD 4 T辅助细胞”，是免疫应答的关键调节剂。这部分是因为这样的T辅助细胞必须被激活，以产生细胞介导的或体液反应。一个中心问题是什么样的情况决定了抗原激活或灭活这些辅助性T细胞？我们正在验证一个假说，试图解释自体抗原和外来抗原如何分别激活和激活相应的辅助性T细胞。这种理解对于制造有效的疫苗非常重要。CD 4辅助性T细胞在确定是否诱导细胞介导或体液应答方面也是至关重要的。细胞介导的应答涉及1型辅助性T细胞或Th 1细胞，抗体应答涉及Th 2细胞。当初始CD 4 T细胞与抗原和免疫系统的其他细胞相互作用时，导致其活化，相互作用的细节决定了是否产生Th 1或Th 2细胞。我们的研究旨在确定到底是什么样的关键和不同的情况下，产生了Th 1和Th 2细胞。在设想如何确保对入侵者作出有效反应时，这一点也很重要。

Our studies are directed at answering two basic questions concerning how immune responses are regulated: what determines whether or not an antigen, foreign or self, launches an immune response when the antigen impinges upon the immune system? Secondly, what determines, if an immune response is launched, the type of immune response, of which there are two major kinds? For example, the immune system can generate a cell-mediated response, consisting of "cytotoxic T cells", that can kill tumor cells or cells infected by a virus, and/or it can produce antibodies that, for example, neutralize toxins that some pathogenic bacteria produce. Remarkably, the immune system has a way of deciding what type of response to generate: a predominant cell-mediated response, a predominant antibody response, or a mixed response. This "decision" is often critical, as different kinds of immunity are effective against different invaders. It has become clear that a cell of the immune system, the "CD4 T helper cell", is a critical regulator of immune responses. This is in part because such T helper cells have to be activated in order for either a cell-mediated or humoral response to be generated. A central question is what circumstances determine whether antigen activates or inactivates these helper T cells? We are testing an hypothesis that tries to explain how self and foreign antigens respectively inactivate and activate their corresponding helper T cells. Such an understanding is important for making effective vaccines. The CD4 T helper cell is also critical in determining whether a cell-mediated or humoral response is induced. Cell-mediated responses involve T helper type 1, or Th1 cells, and antibody responses involve Th2 cells. When a naive CD4 T cell interacts with antigen and other cells of the immune system, resulting in its activation, details of the interactions determine whether Th1 or Th2 cells are generated. Our studies are directed at determining exactly what are the critical and different circumstances that give rise to Th1 and Th2 cells. This is again important in envisaging ways of ensuring an effective response is made against an invader.