Catalina Michelle D, Sullivan John L, Brody Robin M, Luzuriaga Katherine
Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
J Immunol. 2002 Apr 15;168(8):4184-91. doi: 10.4049/jimmunol.168.8.4184.
High frequencies of EBV-specific CD8(+) T cells have been detected during acute EBV infection, yet persistent infection inevitably results. To address this issue, we characterized the phenotype and function of epitope-specific CD8(+) T cell populations from presentation with acute through latent infection. Considerable phenotypic and functional heterogeneity within, as well as between, two different epitope-specific populations was observed over time following acute infection. B7 EBV-encoded nuclear Ag (EBNA)-3A-specific CD8(+) T cells expressed only CD45RO from acute through latent EBV infection. A2 BMLF-1-specific CD8(+) T cells expressed CD45RO during acute infection and either CD45RA or CD45RO during latent EBV infection. This difference in CD45 isoform expression between the two epitope-specific populations did not translate into differences in perforin content, the ability to produce IFN-gamma, or the ability to proliferate in response to Ag in vitro. In individuals with latent EBV infection, the frequencies of A2 BMLF-1- or B7 EBNA-3A-specific CD8(+) T cells that expressed CD45RA, CD45RO, CD62 ligand, CCR7, and perforin were stable over time. However, the expression of CD62 ligand and CCR7 was significantly higher among EBNA-3A-specific CD8(+) T cells than among BMLF-1-specific CD8(+) T cells. Further work is necessary to understand how phenotypic and functional differences between EBV epitope-specific CD8(+) T cells are related to the biology of the virus and to the equilibrium between the virus and the host during persistent infection.
在急性EBV感染期间已检测到高频的EBV特异性CD8(+) T细胞，但仍不可避免地导致持续性感染。为解决这一问题，我们对从急性感染到潜伏感染阶段表位特异性CD8(+) T细胞群体的表型和功能进行了表征。急性感染后，在两个不同的表位特异性群体内部以及之间均观察到相当大的表型和功能异质性。B7 EBV编码核抗原（EBNA）-3A特异性CD8(+) T细胞从急性EBV感染到潜伏感染仅表达CD45RO。A2 BMLF-1特异性CD8(+) T细胞在急性感染期间表达CD45RO，在潜伏EBV感染期间表达CD45RA或CD45RO。这两个表位特异性群体之间CD45异构体表达的差异并未转化为穿孔素含量、产生IFN-γ的能力或体外对抗原刺激增殖能力的差异。在潜伏EBV感染的个体中，表达CD45RA、CD45RO、CD62配体、CCR7和穿孔素的A2 BMLF-1或B7 EBNA-3A特异性CD8(+) T细胞频率随时间保持稳定。然而，EBNA-3A特异性CD8(+) T细胞中CD62配体和CCR7的表达明显高于BMLF-1特异性CD8(+) T细胞。有必要进一步开展研究，以了解EBV表位特异性CD8(+) T细胞之间的表型和功能差异如何与病毒生物学以及持续性感染期间病毒与宿主之间的平衡相关。
