急性病毒感染和慢性病毒感染所引起的CD8+ T细胞反应在动力学、反应数量级和T细胞特异性等方面具有不同特点。近日，美国科学家Miller等人对天花和黄热病疫苗接种者的CD8+ T细胞反应进行了纵向分析。 天花和黄热病疫苗接种可以很好地模拟急性病毒感染的过程，两种疫苗都能很快地引起大量的CD8+ 效应T细胞产生，大约两周达到高峰期。当初次反应达到最高峰，天花和黄热病疫苗特异性的CD8+ T细胞分别占血液中CD8+ T细胞的40%和12.5%。 通过监测EBV-、CMV-以及流感病毒特异性的CD8+ T细胞的反应，证实天花和黄热病疫苗几乎不会引起这些病毒发生特异性CD8+ T细胞的反应，表明无旁观者效应作用。四聚体染色功能分析显示，病毒特异性的CD8+ T细胞首先通过表达穿孔素和颗粒酶B发挥抗病毒效应，紧接着CD8+ 效应T细胞效应进入收缩期，数量减少到高峰期的10%左右，然后逐渐分化成为能够长期存活的CD8+ 记忆性T细胞。组合表型分析发现CD3、CD8、CD38、HLA-DR、Ki67和Bcl-2能够用以鉴定急性病毒感染中效应T细胞的反应，并且效应型T细胞分化成记忆型T细胞的过程是连续性的。（生物谷www.bioon.com） Immunity，Vol 28, 710-722，Joseph D. Miller，Rafi Ahmed Human Effector and Memory CD8+ T Cell Responses to Smallpox and Yellow Fever Vaccines Joseph D. Miller,1,2 Robbert G. van der Most,1,2 Rama S. Akondy,1 John T. Glidewell,1 Sophia Albott,1 David Masopust,1 Kaja Murali-Krishna,1 Patryce L. Mahar,1 Srilatha Edupuganti,1 Susan Lalor,1 Stephanie Germon,1 Carlos Del Rio,1 Mark J. Mulligan,1 Silvija I. Staprans,1,3 John D. Altman,1 Mark B. Feinberg,1,3 and Rafi Ahmed1, 1 Emory Vaccine Center and the Hope Clinic, Emory University School of Medicine, Atlanta, GA 30322, USA Summary To explore the human T cell response to acute viral infection, we performed a longitudinal analysis of CD8+ T cells responding to the live yellow fever virus and smallpox vaccines—two highly successful human vaccines. Our results show that both vaccines generated a brisk primary effector CD8+ T cell response of substantial magnitude that could be readily quantitated with a simple set of four phenotypic markers. Secondly, the vaccine-induced T cell response was highly specific with minimal bystander effects. Thirdly, virus-specific CD8+ T cells passed through an obligate effector phase, contracted more than 90% and gradually differentiated into long-lived memory cells. Finally, these memory cells were highly functional and underwent a memory differentiation program distinct from that described for human CD8+ T cells specific for persistent viruses. These results provide a benchmark for CD8+ T cell responses induced by two of the most effective vaccines ever developed |
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