Pejawar Sharmila S, Parks Griffith D, Alexander-Miller Martha A
Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
J Virol. 2005 Jun;79(12):7544-57. doi: 10.1128/JVI.79.12.7544-7557.2005.
Dendritic cells are the most potent antigen-presenting cell for priming naive T cells. Optimal activation of T cells requires that dendritic cells undergo a process of maturation resulting in the increased expression of costimulatory molecules, such as CD40, CD86, and CD80, and the production of cytokines. In this study we analyzed the effect of infection of dendritic cells obtained from two strains of mice, BALB/c and C57BL/6, with the paramyxovirus simian virus 5 (SV5). Our results show that C57BL/6 bone marrow-derived dendritic cells (BMDC) are much more permissive to infection with SV5 at a multiplicity of infection (MOI) of 10 PFU/cell compared to BALB/c BMDC, as determined by the production of viral proteins and progeny. However, infection of BALB/c BMDC with a higher MOI of 50 PFU/cell resulted in a productive infection with the production of significant amounts of viral proteins and progeny. Regardless of the permissivity to infection, both BALB/c and C57BL/6 BMDC efficiently upregulated CD40 and CD86. However, CD80 upregulation correlated with the level of expression of viral proteins and the production of viral progeny. While secreted alpha/beta interferon was required for increased expression of all three molecules, optimal CD80 expression was dependent on an additional signal provided by a productive viral infection. These findings provide evidence that the signals controlling the expression of costimulatory molecules following viral infection are distinct. Further, they suggest that the amount of virus encountered and/or the permissivity of a dendritic cell to infection can alter the resulting maturation phenotype and functional capacity of the infected dendritic cell.
树突状细胞是启动初始T细胞最有效的抗原呈递细胞。T细胞的最佳激活需要树突状细胞经历一个成熟过程,导致共刺激分子(如CD40、CD86和CD80)表达增加以及细胞因子的产生。在本研究中,我们分析了用副粘病毒猴病毒5(SV5)感染从两种小鼠品系BALB/c和C57BL/6获得的树突状细胞的效果。我们的结果表明,通过病毒蛋白和子代的产生来确定,与BALB/c骨髓来源的树突状细胞(BMDC)相比,C57BL/6骨髓来源的树突状细胞在感染复数(MOI)为10 PFU/细胞时对SV5感染的允许性要高得多。然而,用更高的MOI即50 PFU/细胞感染BALB/c BMDC会导致产生大量病毒蛋白和子代的有效感染。无论对感染的允许性如何,BALB/c和C57BL/6 BMDC均能有效上调CD40和CD86。然而,CD80的上调与病毒蛋白的表达水平和病毒子代的产生相关。虽然分泌的α/β干扰素是所有三种分子表达增加所必需的,但最佳的CD80表达依赖于有效病毒感染提供的额外信号。这些发现提供了证据,表明病毒感染后控制共刺激分子表达的信号是不同的。此外,它们表明遇到的病毒量和/或树突状细胞对感染 的允许性可以改变被感染树突状细胞产生的成熟表型和功能能力。