PRRSV和PCV2共感染对猪肺泡巨噬细胞细胞因子IL-10、IL-12p40和IFN-γ mRNA转录的影响

用猪繁殖与呼吸综合征病毒(PRRSV)和猪圆环病毒2型(PCV2)共感染40日龄健康仔猪,利用实时荧光定量PCR技术对共感染仔猪肺泡巨噬细胞(PAM)细胞因子IL-10、IL-12p40和IFN-γ的mRNA转录水平的变化进行了定量分析。结果表明,IL-12p40 mRNA转录从攻毒后3 d开始显著上调(P<0.05),7 d达高峰,14 d开始下降,但仍显著高于对照组(P<0.05),28 d和42 d低于对照组;IL-10 mRNA在3 d显著上调(P<0.05),14 d达到转录高峰(P<0.01),之后逐渐下降,42 d接近对照组水平;IFN-γmRNA转录水平尽管在3 d和28 d时出现2次转录低峰1、4 d和42 d时出现2次高峰,但只在3 d和7 d差异显著(P<0.05)。由此表明,PRRSV和PCV2共感染可导致PAM细胞因子IL-12p40和IL-10 mRNA的转录在感染早期被激活,而IFN-γ mRNA转录则呈较复杂的动态变化,提示PRRSV和PCV2共感染猪PAM的免疫应答、免疫调节和抗感染功能均受到不同程度的影响。     

PCV2人工感染对猪肺泡巨噬细胞干扰素信号通路的调控研究

通过建立PCV2亚临床感染模型,探究感染仔猪肺泡巨噬细胞中干扰素的变化及其调控,为PCV2复制和发病机制研究提供补充。30日龄猪圆环病毒2型(PCV2)和猪繁殖与呼吸综合征病毒(PRRSV)抗原和抗体均为阴性的仔猪15头,随机分成PCV2阴性对照0d组、PCV2感染14d组和PCV2感染28d组。感染后荧光定量PCR方法检测肺泡巨噬细胞中干扰素、模式识别受体和模式识别受体接头分子mRNA水平。结果显示,IFN-β和IFN-γmRNA转录水平在14和28d均显著高于对照组(P0.05);模式识别受体RIG-1、MDA-5、TLR4和TLR9mRNA转录水平在14和28d显著升高(P0.05);DAI mRNA转录水平在14d显著升高(P0.05),但28d迅速下降;TLR3、TLR7和TLR8mRNA转录水平无明显变化。接头分子MAVS、MyD88、IRF3和IRF7mRNA转录水平在14和28d均显著高于对照组(P0.05)。以上结果表明,PCV2亚临床感染仔猪后导致肺泡巨噬细胞内IFN-β和IFN-γ的表达量上调,其上调和PCV2激活的TLR4/TLR9/MyD88和RIG-1/MDA-5/DAI/MAVS/IRF3信号通路有关。     

PRRSV和PCV2共感染对猪肺泡巨噬细胞CD80-CD86mRNA转录的影响

用猪生殖与呼吸综合征病毒（PRRSV）与猪圆环病毒2型（PCV2）共感染40日龄健康大白仔猪，利用实时荧光定量PCR技术对共感染仔猪肺泡巨噬细胞（PAM）共刺激分子CD80一CD86的mRNA转录水平进行了定量分析。结果表明，在感染后第3d和第7dCD80与CD86mRNA转录显著下调（P〈0．05），感染后第14dCD86mRNA转录水平仍低于未感染对照组。尽管CD80mRNA转录水平在第14d和第28d高于对照组，CD86mRNA转录水平在第28d高于对照组，两者在第42d均高于对照组，但无显著差异。证实，PRRSV和PCV2共感染可导致猪肺泡巨噬细胞的共刺激分子CD80-CD86基因转录在感染早期明显受到抑制，PAM的抗原呈递能力受到影响。     

猪圆环病毒2型感染对猪CD80和CD86 mRNA表达的影响

通过构建猪共刺激分子CD80和CD86的缺失cDNA竞争分子,用竞争PCR技术定量检测了猪圆环病毒2型(PCV2)感染后猪肺泡巨噬细胞(PAM)中CD80和CD86的mRNA水平,分析了PCV2感染对猪共刺激分子CD80和CD86的mRNA表达的影响.结果显示,PCV2感染后,PAM中CD80和CD86的mRNA水平变化趋势一致,只是CD86的升降幅度更大.在PCV2感染后3d,CD80与CD86的mRNA水平下降至最低,随后迅速上升,至14d达到高峰,尔后快速下降,21d及以后恢复正常.本研究结果表明,PCV2初期可明显抑制猪共刺激分子CD80和CD86的基因转录.     

猪圆环病毒2型感染小鼠脾脏内CD4~+CD25~+调节性T细胞的动态变化

为分析猪圆环病毒2型(PCV2)感染小鼠后脾细胞中CD4+CD25+调节性T细胞(Tregs)占CD4+T细胞比例的动态变化,探讨Tregs与PCV2感染的关系,本研究选择清洁级昆明小鼠60只,随机分成实验组和对照组,实验组腹腔接种PCV2,分别在接种后第0 d、5 d、10 d、20 d、30 d和60 d取脾脏制备单细胞悬液,用FITC-CD4和PE-CD25单克隆抗体标记Tregs,采用流式细胞仪检测Tregs占总CD4+T细胞百分比的动态变化。结果表明感染组小鼠脾细胞中Tregs百分比从第5 d开始逐步上升,第20 d达峰值后逐渐下降,感染组Tregs百分比第10 d、20 d、30 d时显著高于对照组(p0.05),但第60 d两组间差异不显著(p0.05)。试验结果证明PCV2感染昆明小鼠后,可在小鼠脾脏内诱导明显的Tregs增殖,这些增殖的细胞可能在PCV2感染中发挥免疫抑制作用。     

利用ICR小鼠模型对PCV2感染中TLR3信号通路的研究

为探究猪圆环病毒2型(PCV2)感染对TLR3信号通路及炎性细胞因子的影响,本研究将30只6周龄ICR雌鼠随机分成两组(感染组和对照组),腹腔接种PCV2b/YJ株,在接种后第7 d、14 d、21 d、28 d和35 d采集小鼠外周血及脾组织。以临床观察、脾组织PCV2基因拷贝、小鼠血清抗体效价、IL-10和TNF-α的mRNA水平等指标评估感染模型;荧光定量PCR检测小鼠脾组织TLR3、TRIF、IFN-β、Mx1的mRNA水平,western blot检测TLR3蛋白表达水平。结果显示:PCV2感染期间感染组小鼠无可见的临床症状,第7 d至35 d感染组小鼠脾组织PCV2基因拷贝数呈逐渐降低趋势,PCV2的IPMA血清抗体在感染后第7 d转阳、35 d达到最高,IL-10 mRNA在感染后第14 d起升高、维持高水平;TNF-αmRNA在感染后第21 d和28 d升高。在感染后第7 d和14 d感染组小鼠TLR3、TRIF mRNA和TLR3蛋白表达水平显著升高;IFN-βmRNA在感染后第7 d具有显著升高过程;Mx1 mRNA在感染后第14 d时有上调过程。本实验在建立PCV2b/YJ亚临床感染ICR小鼠模型的基础上,体内实验表明PCV2感染小鼠激活了TLR3信号通路。本研究为利用敲除小鼠模型阐明TLR3参与PCV2感染引发的免疫应答机制奠定了基础。     

IBDV感染对SPF鸡腔上囊与外周血单核细胞TLR3/4/15mRNA表达的影响

通过点眼将IBDV感染4周龄SPF鸡,采用相对荧光定量PCR技术检测SPF鸡腔上囊单核细胞(BBMC)和外周血单核细胞(PBMC)在感染后不同阶段TLR3/4/15 mRNA表达动态变化,探讨IBDV感染对免疫反应的影响.结果显示,感染后1 d BBMC中TLR3、15的mRNA表达水平高于对照组,差异显著(P≤0.05);在感染后5 d TLR3、4显著高于对照组(P≤0.05);在感染后15 d TLR3/4/15的mRNA表达水平恢复到正常水平.PBMC中,感染后1 d TLR3、4mRNA表达水平均显著高于对照组(P≤0.05),TLR15极显著高于对照组(P≤0.01);而在感染后5d和15 d,TLR3/4均显著高于对照组(P≤0.05).以上结果表明,IBDV感染早期上调了腔上囊和外周血单核细胞的TLR3/4/15的mRNA表达水平,增强了机体的固有免疫反应.     

猪圆环病毒2型感染对猪肺泡巨噬细胞生物学活性的影响

将猪圆环病毒2型（PCV2）BF株经口、鼻接种40日龄健康仔猪，在接种后不同时间宰杀，收集猪肺泡巨噬细胞（PAM），同时设立对照。用FITC—Annexin V／PI双染色流式细胞术和琼脂糖凝胶电泳检测PAM凋亡现象，通过EA花环试验测定Fc受体数目，通过吞噬鸡红细胞试验测定吞噬功能，分析PCV2感染对PAM生物学活性的影响。结果显示，在整个试验期内2种方法均没有检测到PAM凋亡，表明PCV2感染不会诱发PAM凋亡。PAM的Fc受体数和吞噬鸡红细胞数的变化规律一致，与对照组相比，两者数量在接种后第3d明显下降，第7d有所回升，之后基本恢复，表明PCV2感染后PAM吞噬和清除病原的功能出现短暂下降。     

氧化应激对PRRSV致PAM细胞TLR3/NF-κB分子转录的影响

为探讨氧化应激对猪繁殖与呼吸综合征病毒(PRRSV)感染猪肺泡巨噬细胞(PAM)TLR3/NF-κB信号分子转录的影响,体外分离培养PAM,分为对照组、PRRSV感染组、抗氧化剂NAC+PRRSV组,促氧化剂H2O2+RRRSV组。分别在培养6、12、24、48、72h收集细胞,观察各组的细胞病变、real-time PCR检测PRRSV、TLR3、TRIF和NF-κB mRNA转录量的变化。结果显示,PRRSV感染组PRRSV、TLR3、TRIF及NF-κB mRNA的转录量与对照组相比随感染时间的延长显著升高(P0.05),48h达到最大值;NAC处理接毒组各信号分子mRNA的转录量比PRRSV感染组同时间点略低;H_2O_2处理接毒组比PRRSV感染组的略高。结果表明,氧化应激可增强PRRSV致PAM细胞TLR3/NF-κB分子mRNA的转录量,NF-κB的活化可能是PRRSV导致细胞损伤的机制之一。     

猪肺炎支原体对猪肺泡巨噬细胞外源性抗原递呈加工功能相关因子mRNA表达量的影响

将从健康仔猪分离到的猪肺泡巨噬细胞(PAM)分别按1∶10、1∶3和1∶1的比例与猪肺炎支原体(Mhp)232株共同孵育。在孵育12h后收获PAM,用qPCR检测PAM中MHCⅡ分子mRNA表达量,确定PAM和Mhp的最佳孵育比(ROI)。将PAM和Mhp按ROI比例混合孵育(试验组),用等体积的10%RPMI-1640液代替Mhp与PAM孵育作为对照组。分别在孵育后12,24,36,48h收获试验组和对照组的PAM。用实时荧光定量PCR(qPCR)检测PAM中与外源性抗原加工递呈功能相关分子MHCⅡ、SLA-DM、Li和CD86、TLR2和TLR6 mRNA表达量,分析Mhp感染对PAM外源性杭原递呈功能的影响。结果显示:相关因子MHCⅡ、SLA-D、Li、CD86和TLR6在Mhp感染PAM 12h后,mRNA表达量升高(17~380倍);感染24h后降至对照组表达水平的0.043~0.391倍;感染36h后极大地降低;感染后48h全部检测不出。TLR2因子mRNA表达量在Mhp感染12h后降至对照组的0.767倍,感染24h后全部全部检测不出。从检测结果可以看出,Mhp感染早期(12h)可以引起PAM抗原递呈功能相关因子mRNA表达量增加;感染晚期(24h以后)会抑制PAM的外源性抗原递呈加工功能相关因子mRNA表达量。结果表明:Mhp感染早期,动物机体可以通过PAM导致免疫增强,后期会引起免疫抑制。本试验探索了Mhp对PAM外源性抗原加工递呈功能相关因子mRNA表达量影响,为进一步研究Mhp致病机理提供了有益的参考。     

Pattern-recognition receptor mRNA expression and function in canine monocyte/macrophages and relevance to canine anal furunuclosis

Pattern-recognition receptors (PRRs) are important components of the innate immune system, enabling early detection of infection. Defective PRR function has been implicated in several infectious and immune-mediated diseases of human beings, including Crohn's disease (CD). Anal furunculosis (AF) is an immune-mediated disease which primarily occurs in German shepherd dogs (GSD) and could result from a similar type of PRR dysfunction. The aim of the current study was to investigate canine PRR responses in vitro and to test the hypothesis that these were altered in AF-affected GSD. The pattern-recognition receptors TLR1, TLR2, TLR4, TLR6, TLR9, NOD1 (nucleotide-binding oligomerisation domain) and NOD2 were evaluated in the DH82 canine monocyte/macrophage cell line. These cells were found to express mRNA for all the selected PRRs with TLR2 mRNA the most and TLR5 mRNA the least abundant. A similar pattern of expression was found in canine blood-derived monocyte/macrophages. Stimulation of DH82 cells and blood-derived monocyte/macrophages using specific PRR-ligands, resulted in expression of pro-inflammatory cytokine mRNA. Quantification of TNFalpha mRNA and protein secretion from stimulated cells demonstrated variable responses with lipopolysaccharide (TLR4 ligand) and PAM(3)CSK4 (TLR1/2 ligand) proving to be the most potent and CpG DNA (TLR9 ligand) the least potent. Comparing PRR responses in blood-derived monocyte/macrophages from healthy blood-donor dogs with those from AF-affected GSD showed a deficiency in the latter in response to LD-MDP (NOD2 ligand) at the mRNA level but not at the protein level. It is possible that dysfunctional NOD2 responses by cells of the monocyte/macrophage lineage are involved in the pathogenesis of AF.     

Mycoplasma hyopneumoniae bacterins and porcine circovirus type 2 (PCV2) infection: induction of postweaning multisystemic wasting syndrome (PMWS) in the gnotobiotic swine model of PCV2-associated disease

Groups (5 to 15 per group) of gnotobiotic swine were infected oronasally with porcine circovirus type 2 (PCV2) at 3 days of age and then given 1 of 6 different commercial Mycoplasma hyopneumoniae (M. hyopneumoniae) bacterins as either a single dose (7 d of age, 1 application products) or 2 doses (7 and 21 d of age, 2 application product). Control groups received PCV2 alone (n = 9) or were infected with PCV2 and immunized twice with keyhole limpet hemocyanin (KLH) emulsified in incomplete Freund's adjuvant (ICFA) (n = 7). Five of 7 (71%) PCV2-infected piglets immunized with KLH/ICFA developed mild or overt PMWS, whereas none of 9 piglets infected with PCV2 alone developed PMWS. Five of 12 (42%) piglets vaccinated with a commercial bacterin containing mineral oil adjuvant developed PMWS following vaccination. None of the PCV2-infected piglets in the other bacterin-vaccinated groups developed PMWS in this model of PCV2-associated disease. This difference in prevalence of PMWS in piglets given the mineral oil-adjuvanted M. hyopneumoniae bacterin and the other M. hyopneumoniae bacterin vaccination groups was statistically significant (P < 0.05).     

Experimental reproduction of severe disease in CD/CD pigs concurrently infected with type 2 porcine circovirus and porcine reproductive and respiratory syndrome virus

Three-week-old cesarean-derived colostrum-deprived (CD/CD) pigs were inoculated with porcine circovirus type 2 (PCV2, n = 19), porcine reproductive and respiratory syndrome virus (PRRSV, n = 13), concurrent PCV2 and PRRSV (PCV2/PRRSV, n = 17), or a sham inoculum (n = 12) to compare the independent and combined effects of these agents. Necropsies were performed at 7, 10, 14, 21, 35, and 49 days postinoculation (dpi) or when pigs became moribund. By 10 dpi, PCV2/PRRSV-inoculated pigs had severe dyspnea, lethargy, and occasional icterus; after 10 dpi, mortality in this group was 10/11 (91%), and all PCV2/ PRRSV-inoculated pigs were dead by 20 dpi. PCV2-inoculated pigs developed lethargy and sporadic icterus, and 8/19 (42%) developed exudative epidermitis; mortality was 5/19 (26%). PRRSV-inoculated pigs developed dyspnea and mild lethargy that resolved by 28 dpi. Microscopic lesions consistent with postweaning multisystemic wasting syndrome (PMWS) were present in both PCV2- and PCV2/PRRSV-inoculated pigs and included lymphoid depletion, necrotizing hepatitis, mild necrotizing bronchiolitis, and infiltrates of macrophages that occasionally contained basophilic intracytoplasmic inclusion bodies in lymphoid and other tissues. PCV2/ PRRSV-inoculated pigs also had severe proliferative interstitial pneumonia and more consistent hepatic lesions. The most severe lesions contained the greatest number of PCV2 antigen-containing cells. PRRSV-inoculated pigs had moderate proliferative interstitial pneumonia but did not develop bronchiolar or hepatic lesions or lymphoid depletion. All groups remained seronegative to porcine parvovirus. The results indicate that 1) PCV2 coinfection increases the severity of PRRSV-induced interstitial pneumonia in CD/CD pigs and 2) PCV2 but not PRRSV induces the lymphoid depletion, granulomatous inflammation, and necrotizing hepatitis characteristic of PMWS.     

PCV2通过NF-κB/NLRP3信号通路调控体外培养PAMs分泌IL-1β

为探讨猪圆环病毒2型（porcine circovirus 2,PCV2）诱导猪肺泡巨噬细胞（porcine alveolar macrophages,PAMs）产生白细胞介素-1β（interleukin-1β,IL-1β）的分子机制,试验选取2头PCV2和PRRSV抗原、抗体均为阴性的6周龄普通仔猪,无菌分离PAMs,以体外培养的PAMs为研究对象,采用ELISA方法检测PAMs培养上清液中IL-1β的生成,采用实时荧光定量PCR方法检测PAMs中NLRP3和凋亡相关点样蛋白（apoptosis-associated speck-like protein containing a CARD,ASC）的mRNA表达水平,分别用小干扰RNA（siRNA）方法和核因子-kappa B（NF-κB）抑制试验分析NLRP3和NF-κB对PCV2诱导PAMs产生IL-1β的调控作用。结果显示,PCV2感染PAMs后能够显著或极显著增加IL-1β、NLRP3（1 h除外）和ASC（1、3 h除外）的生成（P<0.05;P<0.01）。siRNA能使58.3%的NLRP3基因沉默,且NLRP3沉默后PCV2诱导PAMs产生IL-1β的水平显著下降（P<0.05）。NF-κB被抑制后PCV2诱导PAMs产生IL-1β的水平也明显下降。结果表明,PCV2通过NF-κB/NLRP3信号通路调控体外培养PAMs分泌IL-1β。     

Co-infection of porcine dendritic cells with porcine circovirus type 2a (PCV2a) and genotype II porcine reproductive and respiratory syndrome virus (PRRSV) induces CD4(+)CD25(+)FoxP3(+) T cells in vitro

Porcine circovirus associated disease (PCVAD) is currently one of the most economically important diseases in the global swine industry. Porcine circovirus type 2 (PCV2) is the primary causative agent, however co-infection with other swine pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV) is often required to induce the full spectrum of clinical PCVAD. While the specific mechanisms of viral co-infection that lead to clinical disease are not fully understood, immune modulation by the co-infecting viruses likely plays a critical role. We evaluated the ability of dendritic cells (DC) infected with PRRSV, PCV2, or both to induce regulatory T cells (T(regs)) in vitro. DCs infected with PCV2 significantly increased CD4(+)CD25(+)FoxP3(+) T(regs) (p<0.05) and DCs co-infected with PRRSV and PCV2 induced significantly higher numbers of T(regs) than with PCV2 alone (p<0.05). Cytokine analysis indicated that the induction of T(regs) by co-infected DCs may be dependent on TGF-β and not IL-10. Our data support the immunomodulatory role of PCV2/PRRSV co-infection in the pathogenesis of PCVAD, specifically via T(reg)-mediated immunosuppression.     

猪圆环病毒Ⅱ型体外诱导3D4/2细胞炎症模型的建立

【目的】通过对猪圆环病毒Ⅱ型（PCV2）体外感染3D4/2细胞浓度、时间与细胞炎症水平进行探讨,建立PCV2体外感染3D4/2细胞炎症反应模型,以期为后期药物调控PCV2诱发3D4/2细胞炎症反应的研究奠定基础。【方法】将3D4/2细胞分为对照组及10⁰、10^-1、10^-2和10^-3 PCV2感染组,每组3个重复。对照组用DMEM培养,各PCV2感染组用不同稀释倍数PCV2液培养,2 h后均更换为含5%胎牛血清（FBS）的DMEM维持液进行培养,培养4、8、12和24 h后分别收集细胞及细胞上清液。采用Griess法检测一氧化氮（NO）水平,DCFH-DA荧光探针法检测活性氧（ROS）水平,酶标法检测还原型谷胱甘肽（GSH）水平,分光光度法检测黄嘌呤氧化酶（XOD）和髓过氧化物酶（MPO）活性,ELISA法测定白细胞介素-1β（IL-1β）、IL-6、肿瘤坏死因子-α（TNF-α）、IL-10、γ干扰素（IFN-γ）、IL-8、单核细胞趋化蛋白1（MCP-1）以及环氧合酶1（COX-1）和COX-2的分泌水平。【结果】10⁰至10^-3 PCV2作用4、8、12和24 h均能够成功感染3D4/2细胞。与对照组相比,10⁰ PCV2在感染3D4/2细胞4、8、12、24 h后ROS水平均极显著升高（P<0.01）,10^-1至10^-3 PCV2感染3D4/2细胞8、12、24 h后ROS水平显著或极显著升高（P<0.05;P<0.01）;10⁰至10^-3 PCV2感染3D4/2细胞8、12、24 h后,细胞内NO浓度及MPO活性显著提高（P<0.05）,细胞上清液中的IL-1β、IL-6、TNF-α、IL-10、IFN-γ、IL-8和MCP-1水平及COX-1活性均显著或极显著升高（P<0.05;P<0.01）,其中10⁰ PCV2感染3D4/2细胞后,各炎症因子水平上升最显著,且随着时间的延长,NO浓度逐渐升高,XOD活性逐渐降低。【结论】PCV2可诱导3D4/2细胞炎症反应,且10⁰ PCV2体外感染3D4/2细胞4~12 h是建立炎症模型的最佳条件。     

Expression and function of TLR2, TLR4, and Nod2 in primary canine colonic epithelial cells

The gut maintains a delicate balance between the downregulation of inflammatory reactions to commensal bacteria and the capacity to respond to pathogens with vigorous cellular and humoral immune responses. Intestinal epithelial cells, including colonic epithelial cells (CECs) possess many properties of cells of the innate immune system, in particular the ability to recognize and respond to microbial antigens. Recognition of microorganisms by CECs is based upon their recognition of signature molecules, called microbe-associated molecular patterns (MAMP), by pattern recognition receptors (PRR) including membrane toll-like receptors (TLR) and cytosolic Nod2, an intracellular counterpart of TLRs. The purpose of this study was to determine whether primary CECs from normal dogs express a functional TLR2, TLR4, and Nod2 and whether they are regulated by inflammatory mediators. We show that canine primary CECs express TLR2, TLR4, and Nod2 that can be modulated in response to their respective MAMPs, lipopolysaccharides (LPS) or peptidoglycans (PGN). Furthermore, we demonstrate that these receptors are functional as evidenced by the induction of cytokine gene expression in response to LPS or PGN.     

猪圆环病毒2型感染对伪狂犬疫苗免疫应答的影响

为明确PCV2感染对伪狂犬(PR)疫苗免疫应答的影响,本研究采用阻断ELISA方法对单独接种猪PR疫苗组(A组)及PCV2人工感染3周后接种猪PR疫苗组(PA组)不同时相血清中的猪PR病毒gB抗体进行检测;同时对不同时相前腔静脉血进行CD4+/CD8+流式细胞术及血常规分析。结果表明,在PCV2感染后2周至5周间,A组白细胞含量均高于PA组,随后PA组白细胞恢复至与A组略高的正常水平;在整个实验中,除接种猪PR疫苗后1周(WPI)和9周(WPI)外的所有时相PA组的淋巴细胞含量均略高于A组;PCV2感染后可使记忆/激活Th细胞数量略有升高,幼稚型Th细胞含量的下降;PCV2感染后2周～7周PA组Tc细胞均高于A组,在9WPIPA组Tc细胞数量显著下降(p0.05);除9WPI外,A组的S/N值均低于PA组。结果表明,PCV2感染看降低机体产生针对PRVgB特异性抗体水平,而且在一定程度上降低了幼稚型Th细胞及Tc细胞含量。