CYTOKINE-INDUCED REGULATION OF MATURATION, DIFFERENTIATION, AND APOPTOTIC DEATH OF IMMUNE MEMORY T-LYMPHOCYTES

K. Yurova, D. D. Ligatyuk, D. A. Semenova, L. Litvinova
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Abstract

To maintain the normal state of the immune system, the processes of cell proliferation must be strictly regulated and balanced by the processes of apoptotic death to prevent the development of autoimmune and neoplastic reactions. T-lymphocytes of immune memory are under strict control from the immune system. The role of γc-cytokines (IL-2, IL-7, and IL-15) in the regulation of maturation, differentiation, and apoptotic death of memory T-lymphocytes under in vitro cultivation conditions was evaluated. The study revealed the ability of γc-cytokines to increase the content of CD3+HLA-DR+CD95+ T cells in the effector populations of immune memory cytotoxic lymphocytes, which may indicate the processes of cell differentiation and maturation under the influence of γc-cytokines. The authors also showed that in CD3+CD4+CD45RO+ T-lymphocytes have a relative resistance to the action of γc-cytokines, in comparison with cytotoxic CD45RO+ T-cells. Thus, maintaining homeostatic concentrations of γc-cytokines plays an important role in maintaining the normal functioning of the immune system by maintaining the balance of homeostatic proliferation and apoptotic death. We also noted that cytokine imbalance contributes to an increase in the surface expression of late activation molecules (HLA-DR) and apoptosis (CD95), which is necessary to control excessive proliferation of lymphocytes, and, ultimately, prevents the breakdown of immune tolerance mechanisms and the development of hyperproliferative pathologies of the immune system.
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细胞因子诱导的免疫记忆t淋巴细胞成熟、分化和凋亡的调控
为了维持免疫系统的正常状态,细胞增殖过程必须受到凋亡死亡过程的严格调控和平衡,以防止自身免疫和肿瘤反应的发生。免疫记忆的t淋巴细胞受到免疫系统的严格控制。研究了γ -c细胞因子(IL-2、IL-7和IL-15)在体外培养条件下对记忆t淋巴细胞成熟、分化和凋亡的调控作用。本研究揭示了γ -c细胞因子能够增加免疫记忆细胞毒淋巴细胞效应群体中CD3+HLA-DR+CD95+ T细胞的含量,这可能提示了γ -c细胞因子影响下细胞分化和成熟的过程。作者还表明,与细胞毒性CD45RO+ t细胞相比,CD3+CD4+CD45RO+ t淋巴细胞对γ -c细胞因子的作用具有相对抗性。因此,维持γ -c细胞因子的稳态浓度,通过维持稳态增殖和凋亡死亡的平衡,对维持免疫系统的正常功能起着重要作用。我们还注意到,细胞因子失衡导致晚期活化分子(HLA-DR)和细胞凋亡(CD95)的表面表达增加,这是控制淋巴细胞过度增殖所必需的,并最终防止免疫耐受机制的破坏和免疫系统超增殖病理的发展。
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