IL-12 priming during in vitro antigenic stimulation change's properties of CD8 T cells and increases generation of effector and memory cells
IL-12 priming during in vitro antigenic stimulation change's properties of CD8 T cells and increases generation of effector and memory cells
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DOI：
10.4049/jimmunol.172.5.2818
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Sung, YC
中科院分区：
文献类型：
--
作者：
Chang, J;Cho, JH;Sung, YC
抗原性和共刺激信号触发一个发育程序，通过该程序，初始CD8 T细胞分化为效应细胞和记忆细胞。然而，调节效应CD8 T细胞和记忆CD8 T细胞产生的初始细胞因子信号尚未被充分了解。在这项研究中，我们表明在体外抗原刺激过程中用白细胞介素 - 12（IL - 12）引发，会导致活化细胞过继转移后小鼠的初始和记忆CD8 T细胞群显著增加。IL - 12引发的作用与CD8 T细胞的性质变化密切相关，例如主要组织相容性复合体I（MHC I）四聚体结合减少和CD69表达降低、脂筏分布改变、细胞溶解活性下降以及对细胞凋亡的敏感性降低。此外，外源性IL - 12引发改善了记忆CD8 T细胞的内在存活特性，从而产生更好的保护性免疫以及疫苗诱导的记忆CD8 T细胞反应。然而，对白细胞介素 - 12p40和白细胞介素 - 12受体β1（IL - 12Rβ1）缺陷小鼠的实验表明，与野生型小鼠相比，其初始和记忆CD8 T细胞反应水平相似，这意味着体内内源性IL - 12和/或IL - 12R信号传导对CD8 T细胞免疫并非至关重要。总之，我们的结果表明，IL - 12可作为CD8 T细胞发育的一个重要但非必需的调节因子，并且IL - 12引发在许多医学应用中可能是有用的。
Antigenic and costimulatory signals trigger a developmental program by which naive CD8 T cells differentiate into effector and memory cells. However, initial cytokine signals that regulate the generation of effector and memory CD8 T cells are not well understood. In this study, we show that IL-12 priming during in vitro antigenic stimulation results in the significant increase of both primary and memory CD8 T cell population in mice after adoptive transfer of activated cells. The effect of IL-12 priming is closely associated with qualitative changes in CD8 T cells, such as reduced MHC I tetramer binding and CD69 expression, altered distribution of lipid rafts, decreased cytolytic activity, and less susceptibility to apoptosis. Furthermore, exogenous IL-12 priming improved the intrinsic survival properties of memory CD8 T cells, leading to better protective immunity and vaccine-induced memory CD8 T cell responses. However, the experiments with IL-12p40- and IL-12Rbeta1-deficient mice showed similar levels of primary and memory CD8 T cell responses compared with wild-type mice, implying that endogenous IL-12 and/or IL-12R signaling in vivo is not critical for CD8 T cell immunity. Together, our results suggest that IL-12 can serve as an important, but dispensable regulatory factor for the development of CD8 T cells, and IL-12 priming could be useful in many medical applications.