Cellerai Cristina, Harari Alexandre, Vallelian Florence, Boyman Onur, Pantaleo Giuseppe
Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Eur J Immunol. 2007 Apr;37(4):1129-38. doi: 10.1002/eji.200636885.
The formation of immunological memory is a hallmark of adaptive immunity and the goal of vaccination. For CD8(+ )T cells, successful generation of memory cells has been linked to IL-7 receptor alpha (IL-7Ralpha) expression, suggesting a role for IL-7 signaling, which in turn is important for preventing T cell apoptosis. We thus investigated the kinetics and changes of IL-7Ralpha and anti-apoptotic protein Bcl-2 expression levels in tetanus toxoid (TT)-specific CD4(+ )T cells at different time points prior and after TT re-immunization of TT-immune individuals. Prior to re-immunization, most TT-specific CD4(+ )T cells were high IL-2 producers, CD45RA(-)CCR7(+), IL-7Ralpha(high)Bcl-2(high) cells, resembling typical long-lived central memory cells. Already 5 days, and more importantly at the peak of the response, after TT re-immunization, a substantial fraction of these cells secreted also IFN-gamma, down-regulated CCR7, IL-7Ralpha and Bcl-2 and became Ki67 positive, resembling effector memory cells. In contrast, TT-specific CD4(+ )T cells found 60 days or later after re-immunization were again as baseline. Interestingly, a significant fraction of IL-7Ralpha(high)Bcl-2(high) TT-specific CD4(+ )T cells, i.e. the proposed memory cell precursors, remained stable at any time point upon re-immunization. Together, these results suggest that IL-7Ralpha expression levels might be a useful marker for identifying long-lived Ag-specific CD4(+ )T cells in memory T cells.
免疫记忆的形成是适应性免疫的一个标志，也是疫苗接种的目标。对于CD8(+)T细胞而言，记忆细胞的成功产生与白细胞介素7受体α（IL-7Rα）的表达有关，这表明IL-7信号传导发挥了作用，而IL-7信号传导对于预防T细胞凋亡也很重要。因此，我们研究了破伤风类毒素（TT）免疫个体在再次接种TT之前和之后不同时间点，TT特异性CD4(+)T细胞中IL-7Rα和抗凋亡蛋白Bcl-2表达水平的动力学及变化情况。再次接种前，大多数TT特异性CD4(+)T细胞是高白细胞介素2产生者，为CD45RA(-)CCR7(+)、IL-7Rα(高)Bcl-2(高)细胞，类似于典型的长寿中枢记忆细胞。在再次接种TT后仅5天，更重要的是在反应高峰期，这些细胞中的很大一部分也分泌γ干扰素，CCR7、IL-7Rα和Bcl-2表达下调，并变为Ki67阳性，类似于效应记忆细胞。相比之下，在再次接种后60天或更晚发现的TT特异性CD4(+)T细胞又恢复到基线水平。有趣的是，很大一部分IL-7Rα(高)Bcl-2(高)的TT特异性CD4(+)T细胞，即所谓的记忆细胞前体，在再次接种后的任何时间点都保持稳定。总之，这些结果表明，IL-7Rα表达水平可能是识别记忆T细胞中长寿抗原特异性CD4(+)T细胞的一个有用标志物。
