Centro de Terapia Celular e Molecular, Universidade Federal de São Paulo - Escola Paulista de Medicina São Paulo, São Paulo, Brazil ; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo - Escola Paulista de Medicina São Paulo, São Paulo, Brazil.
Front Immunol. 2012 Dec 4;3:358. doi: 10.3389/fimmu.2012.00358. eCollection 2012.
Owing to the importance of major histocompatibility complex class Ia-restricted CD8(+) T cells for host survival following viral, bacterial, fungal, or parasitic infection, it has become largely accepted that these cells should be considered in the design of a new generation of vaccines. For the past 20 years, solid evidence has been provided that the heterologous prime-boost regimen achieves the best results in terms of induction of long-lived protective CD8(+) T cells against a variety of experimental infections. Although this regimen has often been used experimentally, as is the case for many vaccines, the mechanism behind the efficacy of this vaccination regimen is still largely unknown. The main purpose of this review is to examine the characteristics of the protective CD8(+) T cells generated by this vaccination regimen. Part of its efficacy certainly relies on the generation and maintenance of large numbers of specific lymphocytes. Other specific characteristics may also be important, and studies on this direction have only recently been initiated. So far, the characterization of these protective, long-lived T cell populations suggests that there is a high frequency of polyfunctional T cells; these cells cover a large breadth and display a T effector memory (TEM) phenotype. These TEM cells are capable of proliferating after an infectious challenge and are highly refractory to apoptosis due to a control of the expression of pro-apoptotic receptors such as CD95. Also, they do not undergo significant long-term immunological erosion. Understanding the mechanisms that control the generation and maintenance of the protective activity of these long-lived TEM cells will certainly provide important insights into the physiology of CD8(+) T cells and pave the way for the design of new or improved vaccines.
由于主要组织相容性复合体 I 类限制的 CD8(+) T 细胞对于宿主在病毒、细菌、真菌或寄生虫感染后的存活至关重要，因此人们普遍认为这些细胞应该在新一代疫苗的设计中得到考虑。在过去的 20 年中，已经提供了确凿的证据表明，异源初免-加强方案在诱导针对各种实验性感染的长寿命保护性 CD8(+) T 细胞方面取得了最佳效果。尽管这种方案经常在实验中使用，就像许多疫苗一样，但其疫苗接种方案有效性的机制在很大程度上仍然未知。本综述的主要目的是研究这种疫苗接种方案产生的保护性 CD8(+) T 细胞的特征。其部分功效当然依赖于大量特异性淋巴细胞的产生和维持。其他特定特征也可能很重要，并且最近才开始对此方向进行研究。到目前为止，这些保护性、长寿命 T 细胞群体的特征表明存在高频率的多功能 T 细胞；这些细胞覆盖了广泛的范围，并表现出 T 效应记忆（TEM）表型。这些 TEM 细胞在受到感染性挑战后能够增殖，并且由于控制了凋亡受体如 CD95 的表达，它们对凋亡具有高度抗性。此外，它们不会经历明显的长期免疫侵蚀。了解控制这些长寿命 TEM 细胞的保护性活性的产生和维持的机制，必将为 CD8(+) T 细胞的生理学提供重要的见解，并为设计新的或改进的疫苗铺平道路。
