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Myeloid-like γδ T cell subset in the immune response to an experimental Rift Valley fever vaccine in sheep
Veterinary Immunology and Immunopathology ( IF 1.4 ) Pub Date : 2021-01-08 , DOI: 10.1016/j.vetimm.2021.110184
Maxim Lebedev , Bonto Faburay , Juergen A. Richt , Alan Young

γδ T cells are a numerically significant subset of immune cells in ruminants, where they may comprise up to 70 % of all peripheral blood mononuclear cells (PBMCs) in young animals and 25 % in adults. These cells can be activated through traditional TCR-dependent mechanisms, or alternatively in a TCR-independent manner by pattern recognition receptors and have been shown to uptake antigen, as well as process and present it to αβ T cells. We have identified a novel CD11b+ subset of γδ T cells in normal sheep peripheral blood. An increase in the frequency of these cells in sheep peripheral blood in response to immunization with an experimental recombinant subunit Rift Valley fever (RVF) vaccine was observed. However, injection of the vaccine adjuvant ISA-25VG alone without the recombinant RVF virus antigens demonstrated the same effect, pointing to an antigen-independent innate immune function of CD11b+ γδ T cells in response to the adjuvant. In vitro studies showed repeatable increases of CD11b-, CD14-, CD86-, CD40-, CD72-, and IFNγ- expressing γδ T cells in PBMCs after 24 h of incubation in the absence of a mitogen. Moreover, the majority of these myeloid-like γδ T cells were demonstrated to process exogenous antigen even in the absence of mitogen. ConA activation increased CD25- and MHCII- expression in γδ T cells, but not the myeloid associated receptors CD14 or CD11b or co-stimulatory molecules such as CD86 and CD40. Considering the role of CD11b and CD14 in the activation of innate immunity, we hypothesize that this subpopulation of sheep γδ T cells may function as innate antigen presenting and pro-inflammatory cells during immune responses. The results presented here also suggest that stress molecules and/or damage-associated molecular patterns may be involved in triggering antigen presenting and pro-inflammatory functions of γδ T cells, given their appearance in vitro in the absence of specific stimulation. Taken together, these data suggest that the early appearance of γδ T cells following adjuvant administration and their possible role in early activation of αβ T cell subsets may non-specifically contribute to augmented innate immunity and may promote strong initiation of the adaptive immune response to vaccines in general.



中文翻译:

绵羊裂谷热疫苗免疫反应中的髓样γδT细胞亚群

γδT细胞是反刍动物中免疫细胞的重要数字子集,在年轻的动物中,它们可能占全部外周血单核细胞(PBMC)的70%,在成年动物中占25%。这些细胞可以通过传统的TCR依赖性机制激活,或者通过模式识别受体以TCR依赖性方式激活,并已显示出摄取抗原,并加工并将其呈递给αβT细胞。我们已经鉴定出正常绵羊外周血中γδT细胞的新型CD11b +亚群。观察到,用实验性重组亚基裂谷热(RVF)疫苗免疫后,绵羊外周血中这些细胞的频率增加。但是,单独注射疫苗佐剂ISA-25VG而没有重组RVF病毒抗原,则显示出相同的效果,体外研究表明,在不存在有丝分裂原的情况下孵育24小时后,PBMC中表达CD11b,CD14,CD86,CD40,CD72和IFNγ的γδT细胞可重复增加。此外,这些髓样样γδT细胞大多数被证明即使在没有促细胞分裂剂的情况下也能加工外源性抗原。ConA激活可增加γδT细胞中CD25和MHCII的表达,但不增加与髓系相关的受体CD14或CD11b或共刺激分子(如CD86和CD40)的表达。考虑到CD11b和CD14在先天免疫激活中的作用,我们假设绵羊γδT细胞的这一亚群可能在免疫应答过程中起先天抗原呈递和促炎细胞的作用。没有特异性刺激的体外。综上所述,这些数据表明,佐剂给药后γδT细胞的早期出现及其在αβT细胞亚群的早期激活中的可能作用可能非特异性地促进了先天免疫的增强,并可能促进对疫苗的适应性免疫反应的强烈启动。一般来说。

更新日期:2021-01-14
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