Memory CD8+ T cells require CD28 costimulation
Memory CD8+ T cells require CD28 costimulation
复制标题
DOI：
10.4049/jimmunol.179.10.6494
复制
发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Katsikis, Peter D.
中科院分区：
文献类型：
--
作者：
Borowski, Annie B.;Boesteanu, Alina C.;Katsikis, Peter D.
CD8(+) T细胞是抵抗感染和肿瘤的适应性免疫反应的重要组成部分。当前的免疫学范式是初始CD8(+) T细胞需要CD28共刺激，而记忆CD8+ T细胞不需要。然而，我们在这里表明，在小鼠病毒感染期间，体内需要共刺激来重新激活记忆性CD8(+) T细胞。在缺乏CD28共刺激的情况下，继发性CD8(+) T细胞反应大大降低，这损害了病毒清除。在缺乏CD28共刺激的情况下，CD8+ T细胞的扩张失败是CD4(+) T细胞帮助独立的，并伴随着Bcl-2下调失败和细胞周期停滞。这种对CD28共刺激的需求在甲型流感和HSV感染中都得到了证实。因此，与目前的教条相反，记忆性CD8(+) T细胞需要CD28共刺激才能产生针对病原体的最大二次反应。重要的是，这种CD28需求在真实感染的背景下被证明是多种其他细胞因子和共刺激因子可能上调的。我们的发现对HIV和麻疹病毒等病原体以及通过无法提供CD28共刺激而逃避免疫应答的肿瘤具有重要意义。这些发现也提出了关于CD8(+) T细胞疫苗对这些病原体和肿瘤的有效性的问题。
CD8(+) T cells are a critical component of the adaptive immune response against infections and tumors. A current paradigm in immunology is that naive CD8(+) T cells require CD28 costimulation, whereas memory CD8+ T cells do not. We show here, however, that during viral infections of mice, costimulation is required in vivo for the reactivation of memory CD8(+) T cells. In the absence of CD28 costimulation, secondary CD8(+) T cell responses are greatly reduced and this impairs viral clearance. The failure of CD8+ T cells to expand in the absence of CD28 costimulation is CD4(+) T cell help independent and is accompanied by a failure to down-regulate Bcl-2 and by cell cycle arrest. This requirement for CD28 costimulation was shown in both influenza A and HSV infections. Thus, contrary to current dogma, memory CD8(+) T cells require CD28 costimulation to generate maximal secondary responses against pathogens. Importantly, this CD28 requirement was shown in the context of real infections were multiple other cytokines and costimulators may be up-regulated. Our findings have important implications for pathogens, such as HIV and measles virus, and tumors that evade the immune response by failing to provide CD28 costimulation. These findings also raise questions about the efficacy of CD8(+) T cell-based vaccines against such pathogens and tumors.