Measuring the Immune Memory Response of In Vitro Polarized Th1, Th2, and Th17 Cells in the Face of OVA Transgenic Leishmania major in Mouse Model

bioRxiv Pub Date : 2024-07-16 DOI:10.1101/2024.07.10.601391
Mebrahtu G. Tedla, Musammat F. Nahar, Alison L. Every, Jean-Pierre Y. Scheerlinck
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Abstract

Th1 and Th2 cytokines determine the outcome of Leishmania major infection and immune protection depends mainly on memory T cells induced during vaccination. This largely hinges on the nature and type of memory T cells produced. In this study, transgenic Leishmania major expressing membrane associated ovalbumin (mOVA) and soluble ovalbumin (sOVA) are used as a model to study whether fully differentiated Th1/ Th2 &Th17 cells can recall immune memory and tolerate pathogen manipulation. Naïve OT-II T cells were in vitro polarised into Th1/Th2, and these cells were transferred adoptively into recipient mice. Following transferring the memory cells, recipient mice were challenged with OVA transgenic Leishmania major and wild type parasite was used a control. The in vitro polarised T helper cells continued to produce the same cytokine signatures after challenged by both forms of OVA-expressing Leishmania major parasites in vivo. This suggests antigen-experienced cells cells remain the same or unaltered in the face of OVA transgenic Leishmania major. Such ability of the antigen-experienced cells to remain resilient to manipulation by the parasite signifies that vaccines might be able to produce immune memory responses and withstand against the parasite immune manipulation and protect the host from infection.
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在小鼠模型中测量体外极化 Th1、Th2 和 Th17 细胞对 OVA 转基因利什曼原虫的免疫记忆反应
Th1 和 Th2 细胞因子决定了利什曼原虫感染的结果,而免疫保护主要取决于疫苗接种过程中诱导的记忆 T 细胞。这在很大程度上取决于所产生的记忆 T 细胞的性质和类型。本研究以表达膜相关卵清蛋白(mOVA)和可溶性卵清蛋白(sOVA)的转基因大利什曼原虫为模型,研究完全分化的Th1/Th2和Th17细胞是否能唤起免疫记忆并耐受病原体操作。体外将幼稚的 OT-II T 细胞极化为 Th1/Th2,然后将这些细胞转移到受体小鼠体内。转移记忆细胞后,受体小鼠接受 OVA 转基因大利什曼原虫的挑战,野生型寄生虫则作为对照。体外极化的 T 辅助细胞在体内受到两种形式的表达 OVA 的利什曼原虫挑战后,继续产生相同的细胞因子特征。这表明有抗原经验的细胞在面对 OVA 转基因大利什曼原虫时保持不变或没有改变。抗原经验细胞能够抵御寄生虫的操纵,这意味着疫苗可能能够产生免疫记忆反应,抵御寄生虫的免疫操纵,保护宿主免受感染。
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