Age related human T cell subset evolution and senescence
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Age related human T cell subset evolution and senescence Mingde Li1†, Danlin Yao1†, Xiangbo Zeng1, Dimitri Kasakovski1, Yikai Zhang1, Shaohua Chen1, Xianfeng Zha2, Yangqiu Li1* and Ling Xu1,3*
Abstract T cells are fundamental effector cells against viruses and cancers that can be divided into different subsets based on their long-term immune protection and immediate immune response effects. The percentage and absolute number of these subsets change with ageing, which leads to a reduced immune response in older individuals. Stem cell memory T cells (TSCM) represent a small population of memory T cells with enhanced proliferation and differentiation properties that are endowed with high potential for maintaining T cell homeostasis. However, whether these cells change with ageing and gender remains unknown. Here, we assayed the distribution of TSCM and other T cell subsets in peripheral blood from 92 healthy subjects (44 females and 48 males) ranging from 3 to 88 years old by flow cytometry. We found that CD4+ and CD8+ TSCM in the circulation have relatively stable frequencies, and the absolute number of CD8+ TSCM decreased with age; however, the ratio of TSCM to the CD4+ or CD8+ naïve population increased with age. Unlike the obvious changes in other T cell subsets with age and gender, the stable level of TSCM in peripheral blood may support their capacity for sustaining long-term immunological memory, while their importance may increase together with ageing. Keywords: Stem cell memory T cell, Central memory T cells, Effector memory T cells, Ageing, Immunosenescence
Background Immunosenescence is a complicated process. One discernible alteration is the number and composition of the different types of lymphocytes in the circulation, particularly T cells [1–3]. Conventionally, antigen-exposed T cells have been divided into central memory T (TCM) cells (CD45RO + CCR7+), effector memory T (TEM) cells (CD45RO + CCR7-), and effector T (TEF) cells (CD45RO-CCR7-). With ageing, continuous antigen stimulation and thymic involution lead to a shift in the T cell subset distribution from naïve T cells to TCM, TEM, and TEF [4]. This process is accompanied by the loss of expression of co-stimulatory molecules, such as CD27 and CD28. The results of these changes are likely to be associated with increased susceptibility to infections, autoimmune disorders, chronic diseases, * Correspondence: [email protected]; [email protected] † Mingle Li and Danlin Yao contributed equally to this work. 1 Department of Hematology, First Affiliated Hospital; Institute of Hematology, School of Medicine; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, No.601 West of Huangpu Avenue, Guangzhou 510632, China Full list of author information is available at the end of the article
cardiovascular disease, and even cancers [5–9]. CD28, an important T cell co-stimulatory receptor, is responsible for T cell activation, proliferation, and survival. The accumulation of CD28- T cells, which main
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