Phenotypic and functional heterogeneity of EBV epitope-specific CD8+ T cells

Phenotypic and functional heterogeneity of EBV epitope-specific CD8+ T cells
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DOI:
10.4049/jimmunol.168.8.4184
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发表时间:
2002-04-15
影响因子:
4.4
通讯作者:
Luzuriaga, K
Luzuriaga, K
中科院分区:
医学2区
文献类型:
--
作者:
Catalina, MD;Sullivan, JL;Luzuriaga, K

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在急性EBV感染期间,已经检测到高频率的EBV特异性CD 8(+)T细胞,但持续感染不可避免地导致。为了解决这个问题,我们的特点表位特异性的CD 8(+)T细胞群体的表型和功能,从介绍与急性通过潜伏感染。随着时间的推移,观察到两个不同的表位特异性群体内,以及之间的表型和功能的异质性相当大的急性感染。B7 EBV编码的核Ag(EBNA)-3A特异性CD 8 + T细胞从急性到潜伏性EBV感染仅表达CD 45 RO。A2 BMLF-1特异性CD 8(+)T细胞在急性感染期间表达CD 45 RO,在潜伏性EBV感染期间表达CD 45 RA或CD 45 RO。两个表位特异性群体之间CD 45亚型表达的差异并没有转化为穿孔素含量、产生IFN-γ的能力或体外对Ag应答增殖的能力的差异。在潜伏性EBV感染的个体中,表达CD 45 RA、CD 45 RO、CD 62配体、CCR 7和穿孔素的A2 BMLF-1-或137 EBNA-3A特异性CD 8(+)T细胞的频率随时间推移而稳定。然而,CD 62配体和CCR 7的表达在EBNA-3A特异性CD 8(+)T细胞中显著高于BMLF-1特异性CD 8(+)T细胞。进一步的工作是必要的,以了解EB病毒表位特异性CD 8(+)T细胞之间的表型和功能差异是如何与病毒的生物学和病毒和宿主之间的平衡在持续感染。
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 137 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.