Charerntantanakul Wasin, Platt Ratree, Roth James A
Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
Viral Immunol. 2006 Winter;19(4):646-61. doi: 10.1089/vim.2006.19.646.
The ability of porcine reproductive and respiratory syndrome virus (PRRSV) to suppress T cell expression of CD25 (alpha chain of interleukin [IL]-2 receptor), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) was determined by flow cytometry in naive porcine T cells in response to mitogen (concanavalin A) and cytokine inducers (phorbol 12-myristate 13-acetate plus ionomycin [PMA/I]). Four PRRSV isolates of varying clinical virulence and three different types of porcine myeloid antigen-presenting cells (APCs) were used. T cells cultured with monocytes infected with virulent PRRSV (VR-2385, SDSU-73, and VR-2332), but not with a vaccine strain (Ingelvac PRRS MLV; Boehringer Ingelheim Vetmedica, St. Joseph, MO), demonstrated significantly reduced CD25 expression (%CD25(+)) and IFN-gamma expression (%IFN-gamma (+)) compared with T cells incubated with uninoculated monocyte cultures. T cells cultured with monocytes infected with all four PRRSV isolates demonstrated significantly reduced %TNF-alpha (+). The significant reduction of %CD25(+), %IFN-gamma (+), and %TNF-alpha (+) was not detected in T cells cultured with monocyte-derived macrophages (MDMs) and immature monocyte-derived dendritic cells (MDCs) infected with any PRRSV isolates. Heat-inactivated PRRSV did not induce significantly reduced T cell responses in any APC cultures. The reduction of T cell response in monocyte cultures was not due to PRRSV-induced T cell death. Gene expression of IL-10 detected by semiquantitative reverse transcriptase-polymerase chain reaction was significantly increased in virulent PRRSV-infected monocyte cultures after PMA/I, but not concanavalin A, stimulation compared with IL-10 gene expression from uninoculated monocyte cultures. Increased IL-10 gene expression contributed to significantly reduced %IFN-gamma (+) and %TNF-alpha (+), but not %CD25(+), as determined by IL-10 neutralization assay. This study reports that PRRSV has the ability to suppress T cell responses. The suppressive ability of PRRSV is associated with viral virulence and is mediated by virus-infected monocytes, but not by virus-infected MDMs and immature MDCs.
通过流式细胞术测定了猪繁殖与呼吸综合征病毒（PRRSV）抑制幼稚猪T细胞中CD25（白细胞介素[IL]-2受体α链）、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）表达的能力，这些T细胞对丝裂原（刀豆球蛋白A）和细胞因子诱导剂（佛波酯12-肉豆蔻酸酯13-乙酸酯加离子霉素[PMA/I]）产生反应。使用了四种临床毒力不同的PRRSV分离株和三种不同类型的猪髓系抗原呈递细胞（APC）。与未接种单核细胞培养物孵育的T细胞相比，与感染强毒PRRSV（VR-2385、SDSU-73和VR-2332）的单核细胞共培养的T细胞，而非与疫苗株（Ingelvac PRRS MLV；勃林格殷格翰动物保健公司，密苏里州圣约瑟夫）共培养的T细胞，显示出CD25表达（%CD25(+)）和IFN-γ表达（%IFN-γ(+)）显著降低。与感染所有四种PRRSV分离株的单核细胞共培养的T细胞显示出%TNF-α(+)显著降低。在用感染任何PRRSV分离株的单核细胞衍生巨噬细胞（MDM）和未成熟单核细胞衍生树突状细胞（MDC）培养的T细胞中，未检测到%CD25(+)、%IFN-γ(+)和%TNF-α(+)的显著降低。热灭活的PRRSV在任何APC培养物中均未诱导T细胞反应显著降低。单核细胞培养物中T细胞反应的降低并非由于PRRSV诱导的T细胞死亡。与未接种单核细胞培养物的IL-10基因表达相比，在PMA/I而非刀豆球蛋白A刺激后，通过半定量逆转录聚合酶链反应检测到的强毒PRRSV感染单核细胞培养物中IL-10的基因表达显著增加。如通过IL-10中和试验所确定，IL-10基因表达增加导致%IFN-γ(+)和%TNF-α(+)显著降低，但%CD25(+)未降低。本研究报告PRRSV具有抑制T细胞反应的能力。PRRSV的抑制能力与病毒毒力相关，且由病毒感染的单核细胞介导，而非由病毒感染的MDM和未成熟MDC介导。
