Nielsen J, Bøtner A, Tingstedt J-E, Aasted B, Johnsen C K, Riber U, Lind P
Department of Virology, Danish Veterinary Institute, Lindholm, DK-4771 Kalvehave, Denmark.
Vet Immunol Immunopathol. 2003 Jun 20;93(3-4):135-51. doi: 10.1016/s0165-2427(03)00068-0.
It is well known that piglets congenitally infected with porcine reproductive and respiratory syndrome virus (PRRSV) can be viremic at birth, and that preweaning mortality due to secondary infections often increases during acute outbreaks of PRRS. Therefore, an immunosuppressive effect of in utero infection has been suggested. The aim of the present study was to characterise the changes of leukocyte populations in piglets surviving in utero infection with PRRSV. A total of 27 liveborn uninfected control piglets and 22 piglets infected transplacentally with a Danish strain of PRRSV were included. At 2 and 4 weeks of age, 21 of 22 (96%) and 7 of 14 (50%) examined infected piglets were still viremic, whereas PRRSV could not be detected in the six infected piglets examined at 6 weeks of age. Flow cytometry analysis was used to determine the phenotypic composition of leukocytes in peripheral blood and bronchoalveolar lavage fluid (BALF) of 2-, 4- and 6-week-old infected piglets and age-matched uninfected controls. The key observation in the present study is that high levels of CD8(+) cells constitute a dominant feature in peripheral blood and BALF of piglets surviving in utero infection with PRRSV. In BALF, the average high level of CD8(+) cells in 2-week-old infected piglets (33.4 +/- 12.6%) was followed by a decline to 7.3 +/- 3.0 and 11.1 +/- 3.0% at 4 and 6 weeks of age. BALF of control piglets contained 1.6 +/- 0.9, 2.3 +/- 1.8 and 1.9 +/- 0.5% CD8(+) cells, only. In peripheral blood, however, the average number of CD8(+) cells remained at high levels in the infected piglets throughout the post-natal experimental period (2.8 +/- 1.9, 2.9 +/- 1.8 and 3.2 +/- 1.7 x 10(6) CD8(+) cells/ml at 2, 4 and 6 weeks, respectively). In the controls, the average levels of CD8(+) cells were 0.9+/-0.2, 1.9 +/- 1.7 and 1.6 +/- 0.5 x 10(6)/ml, respectively. Furthermore, the numbers of CD2(+) , CD4(+)CD8(+) and SLA-classII(+) cells, respectively, in peripheral blood, together with the levels of CD2(+) and CD3(+) cells in BALF were increased in the infected piglets infected in utero compared to the uninfected controls. The kinetic analyses carried out in the present study reflect that in utero infection with PRRSV modulates immune cell populations in peripheral blood and BALF of surviving piglets. The observed changes are characterised by high levels of CD8(+) cells supporting an important role of these cells in PRRSV infection. The present results, however, do not support the existence of post-natal immunosuppression following in utero infection with PRRSV.
众所周知,先天性感染猪繁殖与呼吸综合征病毒(PRRSV)的仔猪在出生时即可出现病毒血症,并且在PRRS急性暴发期间,继发感染导致的断奶前死亡率通常会升高。因此,有人提出子宫内感染具有免疫抑制作用。本研究的目的是描述在子宫内感染PRRSV后存活的仔猪白细胞群体的变化。总共纳入了27头出生时未感染的对照仔猪和22头经胎盘感染丹麦株PRRSV的仔猪。在2周龄和4周龄时,22头接受检测的感染仔猪中有21头(96%)和14头中的7头(50%)仍存在病毒血症,而在6周龄接受检测的6头感染仔猪中未检测到PRRSV。采用流式细胞术分析来确定2周龄、4周龄和6周龄感染仔猪以及年龄匹配的未感染对照仔猪外周血和支气管肺泡灌洗液(BALF)中白细胞的表型组成。本研究的关键观察结果是,高水平的CD8(+)细胞是子宫内感染PRRSV后存活仔猪外周血和BALF的主要特征。在BALF中,2周龄感染仔猪CD8(+)细胞的平均高水平(33.4 +/- 12.6%)在4周龄和6周龄时分别降至7.3 +/- 3.0%和11.1 +/- 3.0%。对照仔猪的BALF中仅含有1.6 +/- 0.9%、2.3 +/- 1.8%和1.9 +/- 0.5%的CD8(+)细胞。然而,在整个出生后实验期内,感染仔猪外周血中CD8(+)细胞的平均数量一直保持在高水平(2周龄、4周龄和6周龄时分别为2.8 +/- 1.9×10(6)、2.9 +/- 1.8×10(6)和3.2 +/- 1.7×10(6)个CD8(+)细胞/ml)。在对照组中,CD8(+)细胞的平均水平分别为0.9 +/- 0.2×10(6)/ml、1.9 +/- 1.7×10(6)/ml和1.6 +/- 0.5×10(6)/ml。此外,与未感染对照相比,子宫内感染的感染仔猪外周血中CD2(+)、CD4(+)CD8(+)和SLA - II类(+)细胞的数量以及BALF中CD2(+)和CD3(+)细胞的水平均有所增加。本研究进行的动力学分析表明,子宫内感染PRRSV可调节存活仔猪外周血和BALF中的免疫细胞群体。观察到的变化以高水平的CD8(+)细胞为特征,支持这些细胞在PRRSV感染中起重要作用。然而,本研究结果不支持子宫内感染PRRSV后存在出生后免疫抑制的观点。