Regulation of the function of CD4 T cells

我们的研究旨在回答有关免疫反应如何调节的两个基本问题：是什么决定了抗原，无论是外来的还是自身的，当抗原冲击免疫系统时是否会启动免疫反应？其次，如果发起免疫反应，是什么决定了免疫反应的类型，其中有两种主要类型？例如，免疫系统可以产生细胞介导的反应，包括“细胞毒性T细胞”，可以杀死肿瘤细胞或被病毒感染的细胞，和/或它可以产生抗体，例如，中和一些病原体产生的毒素。值得注意的是，免疫系统有一种方法来决定产生什么类型的反应：主要的细胞介导的反应，主要的抗体反应，还是混合反应。这一“决定”通常是至关重要的，因为不同种类的免疫对不同的入侵者是有效的。很明显，免疫系统的一种细胞，即“CD4T辅助细胞”，是免疫反应的关键调节因素。这在一定程度上是因为这样的T辅助细胞必须被激活，才能产生细胞介导的或体液反应。一个核心问题是，什么情况决定了抗原是激活还是灭活这些辅助T细胞？我们正在测试一个假说，该假说试图解释自身和外来抗原是如何分别灭活和激活相应的辅助T细胞的。这样的理解对于制造有效的疫苗很重要。CD4T辅助细胞在决定是否诱导细胞介导的反应或体液反应方面也是至关重要的。细胞介导的反应涉及辅助性T细胞1，或Th1细胞，抗体反应涉及Th2细胞。当幼稚的CD4T细胞与抗原和免疫系统的其他细胞相互作用，导致其激活时，相互作用的细节决定了Th1细胞或Th2细胞的产生。我们的研究旨在准确确定产生Th1和Th2细胞的关键和不同情况。在设想确保对入侵者作出有效反应的方法时，这一点同样重要。

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.