SUPPRESSOR CELLS (MDSC) REGULATE THE T-CELL RESPONSE IN OLD MICE IMMUNIZED WITH THE WHOLE-VIRION SARS-CoV-2 VACCINE

Y. Perfilyeva, N. Abdolla, A. Kali, R. Tleulieva, D. Aben, Y. Abdusattarova, A. Lushova, Ye. Ostapchuk, B. Karalnik, N. Belyaev
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Abstract

Myeloid-derived suppressor cells (MDSCs) are an immunosuppressive population involved in pathological processes associated with chronic inflammation. In recent years, the role of these cells in the regulation of a number of non-pathological processes, in particular, in the development of vaccine-induced immune response, has been actively discussed. This work was aimed at investigating the role of MDSC in the development of an immune response in old mice immunized with an inactivated whole virion SARS-CoV-2. Immunization of old animals induced an increase in the relative content of B cells and the production of specific antibodies to S1 and N proteins of SARS-CoV-2 in titers comparable to those of young animals. At the same time, elevated MDSC levels in aged animals negatively correlated with the level of CD8+ T cells. Splenic MDSCs in old animals were characterized by increased production of reactive oxygen species compared to young animals. In vitro experiments showed that MDSC depletion increased antigen-specific production of IFNγ  by CD4+ T cells. The data obtained suggest a negative role for MDSC in regulating the T-cell vaccine-induced response to inactivated SARS-CoV-2 and encourage further studies in this direction, which may be a key to developing approaches to increase the efficacy of vaccines against SARS-CoV-2 in at-risk groups.
抑制细胞(MDSC)调节接受全病毒 SARS-CoV-2 疫苗免疫的老龄小鼠的 T 细胞反应
髓源性抑制细胞(MDSCs)是一种免疫抑制细胞,参与了与慢性炎症相关的病理过程。近年来,这些细胞在一些非病理过程中的调控作用,尤其是在疫苗诱导的免疫反应发展过程中的作用得到了积极的讨论。这项工作旨在研究 MDSC 在用灭活全病毒 SARS-CoV-2 免疫老龄小鼠的免疫反应中的作用。免疫老龄动物可诱导 B 细胞相对含量的增加,并产生 SARS-CoV-2 S1 和 N 蛋白特异性抗体,其滴度与年轻动物相当。同时,老年动物体内 MDSC 水平的升高与 CD8+ T 细胞水平呈负相关。与年轻动物相比,老年动物脾脏MDSC的特点是活性氧生成增加。体外实验表明,MDSC 的消耗增加了 CD4+ T 细胞产生的抗原特异性 IFNγ。所获得的数据表明,MDSC在调节T细胞对灭活SARS-CoV-2疫苗诱导的反应中起着负面作用,并鼓励朝这个方向进一步研究,这可能是开发提高高危人群SARS-CoV-2疫苗疗效的关键。
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