Byers Anthony M, Andrews Nicolas P, Lukacher Aron E
Department of Pathology, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322, USA.
J Immunol. 2006 May 15;176(10):6121-9. doi: 10.4049/jimmunol.176.10.6121.
Memory CD8 T cells comprise a critical component of durable immunity because of their capacity to rapidly proliferate and exert effector activity upon Ag rechallenge. During persistent viral infection, memory CD8 T cells repetitively encounter viral Ag and must maintain a delicate balance between limiting viral replication and minimizing immunopathology. In mice infected by polyoma virus, a natural mouse pathogen that establishes long-term persistent infection, the majority of persistence-phase antiviral CD8 T cells express the inhibitory NK cell receptor CD94/NKG2A. In this study, we asked whether CD94/NKG2A expression is associated with Ag-specific recall of polyoma virus-specific CD8 T cells. During the persistent phase of infection, polyoma virus-specific CD8 T cells that express CD94/NKG2A were found to preferentially proliferate; this proliferation was dependent on cognate Ag both in vitro and in vivo. In addition, CD94/NKG2A(+) polyoma-specific CD8 T cells have a markedly enhanced capacity to produce IL-2 upon ex vivo Ag stimulation compared with CD94/NKG2A(-) polyoma-specific CD8 T cells. Importantly, CD94/NKG2A(+) anti-polyoma virus CD8 T cells appear to be essential for Ag-specific recall responses in mice persistently infected by polyoma virus. Because of its higher proliferative potential and capacity to produce IL-2, we propose that the CD94/NKG2A(+) subpopulation represents a less differentiated state than the CD94/NKG2A(-) subpopulation. Identification of proliferation-competent subpopulations of memory CD8 T cells should prove valuable in designing therapeutic vaccination strategies for persistent viral infections.
记忆性CD8 T细胞是持久免疫的关键组成部分，因为它们能够迅速增殖并在再次接触抗原时发挥效应活性。在持续性病毒感染期间，记忆性CD8 T细胞反复接触病毒抗原，必须在限制病毒复制和最小化免疫病理之间保持微妙的平衡。在感染多瘤病毒（一种能建立长期持续性感染的天然小鼠病原体）的小鼠中，大多数持续性抗病毒CD8 T细胞表达抑制性NK细胞受体CD94/NKG2A。在本研究中，我们探讨了CD94/NKG2A的表达是否与多瘤病毒特异性CD8 T细胞的抗原特异性回忆有关。在感染的持续阶段，发现表达CD94/NKG2A的多瘤病毒特异性CD8 T细胞优先增殖；这种增殖在体外和体内均依赖于同源抗原。此外，与CD94/NKG2A（-）多瘤病毒特异性CD8 T细胞相比，CD94/NKG2A（+）多瘤病毒特异性CD8 T细胞在体外抗原刺激后产生IL-2的能力明显增强。重要的是，CD94/NKG2A（+）抗多瘤病毒CD8 T细胞似乎对多瘤病毒持续感染小鼠的抗原特异性回忆反应至关重要。由于其更高的增殖潜力和产生IL-2的能力，我们提出CD94/NKG2A（+）亚群比CD94/NKG2A（-）亚群代表一种分化程度较低的状态。鉴定具有增殖能力的记忆性CD8 T细胞亚群在设计针对持续性病毒感染的治疗性疫苗策略方面应具有重要价值。
