Morimura T, Hattori M, Ohashi K, Sugimoto C, Onuma M
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
J Gen Virol. 1995 Dec;76 ( Pt 12):2979-85. doi: 10.1099/0022-1317-76-12-2979.
Marek's disease virus (MDV) causes T cell immunosuppression in chickens during latent infection. Morphological changes specific to apoptosis were demonstrated in peripheral blood mononuclear cells (PBMC) of MDV-infected chickens at 2-3 weeks post-inoculation (p.i.). Analysis of DNA fragmentation in T cell subsets in the peripheral blood revealed that CD4+ T cells but not CD8+ T cells underwent apoptosis after MDV infection. The proportion of CD4+ T cells, but not that of CD8+ T cells, in the peripheral blood expanded transiently at 16 days p.i., and rapidly decreased 1 week later. The decrease in CD4+ T cells might be mediated by apoptosis, because a rapid reduction in CD4+ T cells was observed when these cells underwent apoptosis. Analysis of the T cell-receptor (TCR) repertoire of the peripheral blood showed that V beta 1 but not V beta 2-alpha beta TCR-bearing cells expanded at 16 days p.i., when the transient expansion of the CD4+ T cell population was observed in these chickens. Flow cytometric profiles also showed that the expression of CD8 was down-regulated after infection with MDV, but there was no difference in the expression level of CD4 molecules between normal and infected chickens. Northern blot analysis indicated that the down-regulation of CD8 occurred at the transcriptional level. These results suggest that both apoptosis of CD4+ T cells and down-regulation of CD8 molecules could contribute to the immunosuppression caused by MDV.
马立克氏病病毒(MDV)在潜伏感染期间会导致鸡的T细胞免疫抑制。在接种后2 - 3周,MDV感染鸡的外周血单核细胞(PBMC)中出现了特定于细胞凋亡的形态学变化。对外周血中T细胞亚群的DNA片段化分析显示,MDV感染后CD4⁺ T细胞而非CD8⁺ T细胞发生凋亡。外周血中CD4⁺ T细胞的比例在接种后16天短暂增加,1周后迅速下降,而CD8⁺ T细胞的比例没有变化。CD4⁺ T细胞的减少可能是由细胞凋亡介导的,因为当这些细胞发生凋亡时观察到CD4⁺ T细胞迅速减少。对外周血T细胞受体(TCR)库的分析表明,在接种后16天,当观察到这些鸡的CD4⁺ T细胞群体短暂增加时,携带Vβ1而非Vβ2 - αβ TCR的细胞增加。流式细胞术分析还显示,MDV感染后CD8的表达下调,但正常鸡和感染鸡之间CD4分子的表达水平没有差异。Northern印迹分析表明CD8的下调发生在转录水平。这些结果表明,CD4⁺ T细胞的凋亡和CD8分子的下调都可能导致MDV引起的免疫抑制。