受体相互作用蛋白激酶-3(receptor-interacting protein kinase 3, RIPK3)是坏死复合体的关键成分之一,介导细胞程序性死亡(programmed cell death,PCD)的发生。前期研究发现流感抗原特异性CD8+T细胞的初次应答部分依赖于RIPK3分子,为探讨其在记忆性CD8+T细胞应答中的作用,对初次感染后的C57BL/6小鼠在免疫记忆阶段进行了再次感染,并用流式细胞仪检测了流感病毒特异性的记忆性CD8+T细胞的表型和功能。结果发现小鼠初次感染甲型 H1N1流感病毒株A/Puerto Rico/8/34后37 d, RIPK3敲除小鼠的CD8+T细胞比例及分泌细胞因子γ-干扰素(IFN-γ)和肿瘤坏死因子-α(TNF-α)的能力均显著低于野生型小鼠;在再次感染相同病毒时,RIPK3敲除小鼠流感病毒特异性CD8+T细胞比例及分泌细胞因子IFN-γ的能力依旧显著低于野生型小鼠;而CD8+中枢型记忆性T细胞(TCM)比例显著高于野生型小鼠,效应型记忆性T细胞(TEM)或效应性T细胞(TEff)比例却显著低于野生型小鼠。提示RIPK3分子参与调节流感病毒特异的记忆性CD8+T细胞诱生数量和分泌细胞因子功能,并影响其TCM与TEM/TEff的比例,为深入探索病毒特异的记忆性CD8+T细胞应答的分子机制提供了新线索。
Receptor-interacting protein kinase 3 (RIPK3) is one of the key components of necrotic complex, which mediates the development of programmed cell necrosis. Our previous studies have revealed that the initial response of total influenza antigen-specific CD8+T cells is partially dependent on RIPK3, but its role in memory CD8+T cell response is unclear yet. In this study, we observed that the frequency of influenza specific CD8+T cells and their ability to secrete cytokine IFN-γ and TNF-α in RIPK3 knockout mice were significantly lower than those in wild-type mice 37 days after the initial infection of H1N1 A/Puerto Rico/8/34 strain (PR8) in C57BL/6 mice. After the re-challenging infection of H1N1virus PR8, the frequency of viral specific CD8+T cells and their ability to secrete cytokine IFN-γ in RIPK3 knockout mice were still significantly lower than those in wild-type mice. In addition, while the frequency of CD8+central memory T cells (TCM) in RIPK3 knockout mice was significantly higher than that in wild-type mice, the proportion of effective memory T cells (TEM) or effective T cells (TEff) was significantly lower than that in wild-type mice. These results indicate that RIPK3 is involved in the regulation of the number and secretion of cytokines of influenza virus specific memory CD8+T cells, and affects the ratio of TCM to TEM or TEff in memory CD8+T cells, which provide new clues for further exploring the molecular mechanism of virus specific memory CD8+T cell response.