Factors Regulating T Helper Cell Memory Differentiation

CD4+ T细胞可以根据其细胞因子产生的模式划分为不同的亚群。分泌IFN-g的CD4+ T细胞称为Th1细胞，分泌IL-4、IL-5和IL-13的细胞称为Th2细胞。虽然Th1细胞在介导多种细胞内感染的保护中至关重要，但它们也介导与多种自身免疫性疾病相关的促炎症反应。Th2细胞在反调节Th1反应中起作用，并与过敏性和哮喘疾病有关。这些研究检查了调节T辅助反应如何在体内维持的因素。最近的研究探索了CD4+/IFN-g效应细胞在体内死亡的机制。这项工作研究了不同谱系的Th1细胞在抗原刺激下在体内存活的能力。研究了分泌IL-2和IFN-g能力不同的Th1细胞群。一个主要的重点是了解这些细胞群在体内如何被调节的差异。过去一年的研究结果如下：

CD4+ T cells can be segregated into distinct subsets based on their pattern of cytokine production. CD4+ T cells that secrete IFN-g are termed Th1 cells while cells that secrete IL-4, IL-5 and IL-13 are termed Th2 cells. While Th1 cells are essential in mediating protection against a variety of intracellular infections they also mediate pro-inflammatory responses associated with a variety of autoimmune diseases. Th2 cells have a role in counter-regulating Th1 responses and are associated with allergic and asthmatic disease. These studies examine the factors, which regulate how T helper responses are sustained in vivo. Recent work explores the mechanism by which CD4+/IFN-g effector cells die in vivo. The work studies the capacity of distinct lineages of Th1 cells to survive in vivo following antigenic stimulation. Populations of Th1 cells which differ in their ability to secrete IL-2 and IFN-g are studied. A major emphasis is to understand differences in how these populations of cells are regulated in vivo. The studies over the past year have shown the following: 1. Th1 effector cells are killed in vivo in an IFN-g dependent manner. 2. IFN-g mediates death of Th1 effector cells indirectly and not in an autocrine manner. 3. Th1 cells have a linear transition from effector cells secreting IFN-g and IL-2 to IFN-g only and then death.