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产犊前后免疫反应偏向的奶牛中CD4 + T细胞的I型和II型细胞因子产生

Type I and type II cytokine production of CD4+ T-cells in immune response biased dairy cattle around calving.

作者信息

Paibomesai M A, Sharif S, Karrow N, Mallard B A

机构信息

Dept. of Pathobiology, Ontario Veterinary College , University of Guelph, Guelph, Ontario, N1G 2W1, Canada; Ontario Ministry of Agriculture, Food and Rural Affairs, 1 Stone Road West, Guelph, Ontario, Canada.

Dept. of Pathobiology, Ontario Veterinary College , University of Guelph, Guelph, Ontario, N1G 2W1, Canada.

出版信息

Vet Immunol Immunopathol. 2018 May;199:70-76. doi: 10.1016/j.vetimm.2018.03.001. Epub 2018 Mar 3.

DOI:10.1016/j.vetimm.2018.03.001
PMID:29678232
Abstract

The peripartum period is a period of high stress, transition and management changes for dairy cows. It is associated with higher incidence of both metabolic and pathogenic disease. Both antibody-(AMIR) and cell-(CMIR) mediated immune responses play a key role in the maintenance of health in mammals protecting against extracellular and intracellular pathogens, respectively. Generally, interferon gamma (IFN-γ) has been associated with CMIR, whereas interleukin 4 (IL-4) has been associated with AMIR bias, and interleukin 17 (IL-17A) is associated with pro-inflammatory. It has been previously demonstrated that cows can be classified as high (H), average (A), and low (L) immune responders based upon their AMIR and CMIR to test antigens, and that this classification is associated with disease occurrence throughout lactation. The mechanisms behind these differences in phenotype and the effects of the peripartum period have not been fully investigated. The aim of this study was to determine the effects of the peripartum period on cytokine production of CD4+ T-cells or T helper (Th) cells, key mediators of the adaptive immune response. Immune response phenotyped cows were selected based on H-AMIR/L-CMIR (H-AMIR cows; n = 10) and H-CMIR/L-AMIR (H-CMIR cows; n = 11) response to test antigens. Isolated CD4+ T-cells collected at 28 days before calving (prepartum samples), 4 days after calving (early postpartum samples), and 21 days after calving (late postpartum samples) from these groups were stimulated with Concanavalin-A (ConA) with unstimulated controls. Subsequently, IL-4, IFN-γ, and IL-17A concentrations were quantified by ELISA. Overall, there was no obvious decline in IL-4, IFN-γ or IL-17A close to calving observed from CD4+ T-cells from each of these phenotypically distinct groups of cows. However, CD4+ T-cells isolated from H-CMIR secreted higher amounts of IL-4 (746.43 ± 428 pg/mL), IL-17A (446IL ± 62 pg/mL), and IFN-γ (7755.79 ± 4449 pg/mL) than H-AMIR cows (IL-4 (212.15 ± 121 pg/mL), IL-17A (163.15 ± 87 pg/mL), and IFN-γ (2909.771 ± 1671 pg/mL)) on day 21 after calving, late postpartum. This study indicates a genetic predisposition based on immune response phenotype of cytokine production from CD4+ T-cells around calving.

摘要

围产期对奶牛来说是一个压力大、处于过渡阶段且管理方式发生变化的时期。它与代谢性疾病和致病性疾病的较高发病率相关。抗体介导的免疫反应(AMIR)和细胞介导的免疫反应(CMIR)分别在哺乳动物抵御细胞外和细胞内病原体以维持健康方面发挥关键作用。一般来说,γ干扰素(IFN-γ)与CMIR相关,而白细胞介素4(IL-4)与AMIR偏向相关,白细胞介素17(IL-17A)与促炎反应相关。先前已经证明,根据奶牛对测试抗原的AMIR和CMIR,可将其分为高(H)、中(A)、低(L)免疫应答者,并且这种分类与整个泌乳期的疾病发生情况相关。这些表型差异背后的机制以及围产期的影响尚未得到充分研究。本研究的目的是确定围产期对CD4 + T细胞或辅助性T(Th)细胞细胞因子产生的影响,这些细胞是适应性免疫反应的关键介质。根据对测试抗原的H-AMIR/L-CMIR(H-AMIR奶牛;n = 10)和H-CMIR/L-AMIR(H-CMIR奶牛;n = 11)反应选择免疫反应表型的奶牛。从这些组中在产犊前28天(产前样本)、产犊后4天(产后早期样本)和产犊后21天(产后晚期样本)采集的分离CD4 + T细胞用伴刀豆球蛋白A(ConA)刺激,并设置未刺激的对照。随后,通过酶联免疫吸附测定(ELISA)对IL-4、IFN-γ和IL-17A浓度进行定量。总体而言,从这些表型不同的奶牛组的CD4 + T细胞中未观察到接近产犊时IL-4、IFN-γ或IL-17A有明显下降。然而,在产后晚期(产犊后21天),从H-CMIR分离的CD4 + T细胞分泌的IL-4(746.43±428 pg/mL)、IL-17A(446±62 pg/mL)和IFN-γ(7755.79±4449 pg/mL)比H-AMIR奶牛(IL-4(212.15±121 pg/mL)、IL-17A(163.15±87 pg/mL)和IFN-γ(2909.771±1671 pg/mL))更多量。本研究表明,产犊前后CD4 + T细胞细胞因子产生的免疫反应表型存在基于遗传的易感性。

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