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CD8+CD28- T cells: not only age-related cells but a subset of regulatory T cells

Cellular & Molecular Immunology volume 15, pages 734–736 (2018)Cite this article

CD28 serves as a co-stimulator for T-cell activation and survival, and is expressed on all naive T cells in newborns.1 However, as T cells experience antigen-mediated activation and differentiation, they gradually lose CD28 expression.2 The age-related increase of CD28− T cells in human peripheral blood means that immune function declines in the elderly.1 Among the populations of CD28- T cells, CD8+CD28- T cells show the greatest age-related increase.1 These cells, which were first described in aged humans, exhibit weak immune-responsiveness and shortened telomeres and are often considered to exhibit age-associated replicative senescence.3 To date, CD8+CD28- T-cell alterations have been reported in cancer, viral infections, autoimmunity and almost every chronic inflammatory disease.3,4

Recently, CD8+CD28- T cells have attracted interest because of their critical roles in immunomodulation. Suciu-Foca et al. 5 first described CD8+CD28- T cells as a subset of suppressor cells within the CD8+ T-cell population. Growing evidence suggests that CD8+CD28- T cells are a unique subpopulation of regulatory T cells (Tregs) that exert broad effects on directly regulating T cells, such as by inhibiting their activation and proliferation, decreasing the secretion of proinflammatory cytokines by activated T cells, and inducing apoptosis in activated T cells in vitro.6,7 Cell contact and soluble factors, including TGF-β, IL-7, IL-10, PDL-1 and FasL, contribute to the ability of CD8+CD28- T cells to regulate T-cell responses.6,7 Moreover, CD8+CD28- T cells may indirectly control T-cell responses, such as by up-regulating LILRB4 and LILRB2 on antigen-presenting cells (APCs), which gives rise to tolerogenic APCs that have an impaired capacity for co-stimulating T-cell activation.3,8 Tolerized APCs also interact with naive CD8+ T cells, induce their expression of Foxp3 and promote their development into CD8+CD28-Foxp3+ T cells,8 which comprise the major subset of CD8+CD28- Tregs.

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Acknowledgements

The work is supported by grant from the National Key Research and Development Program of China, Stem Cell and Translational Research (2017YFA0103403, 2017YFA0105504); the National Natural Science Foundation of China (81425016, 81600102, 81601381, 31771616, 81730005); the Natural Science Foundation of Guangdong Province (S2013030013305, 2016A030310131); the Key Scientific and Technological Projects of Guangdong Province (2014B020226002, 2015B020228001, 2015B020229001, 2016A020214003, 2016B030229002); Key Scientific and Technological Program of Guangzhou City (201508020262, 201704020223); Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS, 2013).

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  1. These authors contributed equally to this work.

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  1. Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China

    Xiaoyong Chen & Andy Peng Xiang

  2. The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Qiuli Liu

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Correspondence to Andy Peng Xiang.

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Chen, X., Liu, Q. & Xiang, A.P. CD8+CD28- T cells: not only age-related cells but a subset of regulatory T cells. Cell Mol Immunol 15, 734–736 (2018). https://doi.org/10.1038/cmi.2017.153

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