Factors Regulating T Helper Cell Memory Differentiation

根据细胞因子的产生模式，可以将CD4+T细胞分为不同的亚群。分泌干扰素-g的CD4+T细胞称为Th1细胞，而分泌IL-4、IL-5和IL-13的细胞称为Th2细胞。虽然Th1细胞在介导对各种细胞内感染的保护方面是必不可少的，但它们也介导了与各种自身免疫性疾病相关的促炎反应。Th2细胞具有反向调节Th1反应的作用，并与过敏性和哮喘疾病有关。这些研究考察了调节T辅助反应如何在体内持续的因素。最近的工作探索了CD4+/干扰素-g效应细胞在体内死亡的机制。这项工作研究了不同血统的Th1细胞在抗原刺激后在体内存活的能力。研究了分泌IL-2和干扰素-g能力不同的Th1细胞群体。一个主要的重点是了解这些细胞群体在体内如何调节的差异。过去一年的研究显示： 1.Th1细胞从只分泌干扰素-γ和白介素2的效应细胞向只分泌干扰素-γ的效应细胞线性过渡，然后死亡。 2.经过多次刺激的Th1细胞在受到单核细胞增多性李斯特菌的攻击时，比只经历一轮激活的细胞具有更好的保护作用。然而，重复刺激的细胞寿命并不长。 3.细胞内蛋白如FOXO-3a和BIM在不同的Th1细胞群体中差异表达。这些蛋白的表达与细胞死亡和重复刺激的Th1细胞的记忆能力有限有关。

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 cells have a linear transition from effector cells secreting IFN-g and IL-2 to IFN-g only and then death. 2. Th1 cells that have been repetitively stimulated confer better protection upon challenge with Listeria monocytogenes than cells that have undergone only one round of activation. However, repetitively stimulated cells are not long-lived. 3. Intracellular proteins such as Foxo-3a and BIM are differentially expressed in distinct populations of Th1 cells. Expression of such proteins correlate with cell death and limited memory capacity of repetitively stimulated Th1 cells.