Cytokine response in multiple lymphoid tissues during the primary phase of feline immunodeficiency virus infection

Cytokine response in multiple lymphoid tissues during the primary phase of feline immunodeficiency virus infection
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DOI:
10.1128/jvi.72.12.9436-9440.1998
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发表时间:
1998-12-01
影响因子:
5.4
通讯作者:
Pedersen, NC
Pedersen, NC
中科院分区:
医学2区
文献类型:
--
作者:
Dean, GA;Pedersen, NC

文献摘要

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1型和2型细胞因子mRNA的反应,测定在不同的时间段和在不同的淋巴室在急性阶段(前4个月)的猫免疫缺陷病毒(FIV)感染的实验室猫。细胞因子应答与病毒复制相关。从感染后(p.i.)在56 - 70天达到高峰,70天后急剧下降。病毒在胸腺中复制最高,其次是脾脏、肠系膜淋巴结和颈淋巴结。基线细胞因子水平在肠系膜淋巴结中最高,在颈部淋巴结中最低。FIV感染后细胞因子的上调在颈部淋巴结中最为显著,其中白细胞介素-10(IL-10)和γ干扰素(IFN-γ)的增加最大。到感染后第14天,肠系膜淋巴结中的细胞因子转录增加至高于基线。IFN-γ、IL-12 p40、IL-4和IL-10的升高,而脾脏中的升高主要是IFN-γ、IL-12 p40和IL-10。免疫后第56天,胸腺中IFN-γ、IL-10和IL-12 p40增加,伴随着胸腺炎的发作。一般而言,2型细胞因子(IL-4和IL-10)相对于基线增加大于1 log,而1型细胞因子的升高小于1 log。在检测的组织中,CD 4(+)细胞是IL-2、IL-4和IL-10的主要来源。CD 4(+)和CD 8(+)细胞均产生IFN-γ,而B细胞中未检测到细胞因子mRNA。这些结果表明,在FIV感染的初级阶段,淋巴组织中存在异质性细胞因子应答。反应的性质和强度因隔室而异,在胸腺中也有炎症变化。虽然范围有限,但本研究证实了FIV感染模型在研究导致大多数慢病毒感染典型的继发亚临床携带状态的早期细胞因子事件中的有用性。
Type 1 and 2 cytokine mRNA responses were measured at various time periods and in various lymphoid compartments during the acute stage (first 4 months) of feline immunodeficiency virus (FIV) infection in laboratory cats. Cytokine responses were correlated with virus replication. Virus was detected in plasma and tissue from day 14 postinfection (p.i.) onward, peaked at 56 to 70 days, and declined greatly by 70 days. Virus replication was highest in the thymus, followed by spleen, mesenteric lymph nodes, and cervical lymph nodes. Baseline cytokine levels were highest in the mesenteric lymph nodes and lowest in the cervical lymph nodes. Cytokine upregulation after FIV infection was most dramatic in the cervical lymph nodes, with the greatest increase in interleukin-10 (IL-10) and gamma interferon (IFN-gamma). Cytokine transcription in the mesenteric lymph node increased above baseline by day 14 p.i. for IFN-gamma, IL-12p40, IL-4, and IL-10, while elevations in the spleen were mainly for IFN-gamma, IL-12p40 and IL-10. An increase in IFN-gamma, IL-10, and IL-12p40 occurred in the thymus at day 56 p.i., concomitant with the onset of thymitis. In general, type 2 cytokines (IL-4 and IL-10) were increased greater than 1 log over baseline, while the elevations in type 1 cytokines were less than 1 log. In the tissues tested, CD4(+) cells were the primary source of IL-2, IL-4, and IL-10. Both CD4(+) and CD8(+) cells produced IFN-gamma, while no cytokine mRNA was detected in B cells. These results demonstrate the presence of a heterogeneous cytokine response in lymphoid tissues during the primary stage of FIV infection. The nature and intensity of the response differed from one compartment to the other and, in the case of the thymus, also with inflammatory changes. Although limited in scope, the present study confirms the usefulness of the FIV infection model in studying early cytokine events that lead to the secondary subclinical carrier state typical of most lentivirus infections.