title: Glimpse of natural selection of long-lived T-cell clones in healthy life.
abstract: Homeostatic maintenance of T cells with broad clonal diversity is influenced by both continuing output of young T cells from the thymus and ongoing turnover of preexisting clones in the periphery. In the absence of infection, self and commensal antigens are thought to play important roles in selection and homeostatic maintenance of the T-cell pool. Most naïve T cells are short-lived due to lack of antigen encounter, whereas antigen-experienced T cells may survive and persist as long-lived clones. Thus far, little is known about the homeostasis, antigenic specificity, and clonal diversity of long-lived T-cell clones in peripheral lymphoid organs under healthy living conditions. To identify long-lived T-cell clones in mice, we designed a lineage-tracing method to label a wave of T cells produced in the thymus of young mice. After aging the mice for 1.5 y, we found that lineage-tracked T cells consisted of primarily memory-like T cells and T regulatory cells. T-cell receptor repertoire analysis revealed that the lineage-tracked CD4 memory-like T cells and T regulatory cells exhibited age-dependent enrichment of shared clonotypes. Furthermore, these shared clonotypes were found across different mice maintained in the same housing condition. These findings suggest that nonrandom and shared antigens are involved in controlling selection, retention, and immune tolerance of long-lived T-cell clones under healthy living conditions.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Baojun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Biomedical Analysis Center, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Cheryl
authors.initials: C
authors.lastname: Bock
authors.affiliation: Biomedical Analysis Center, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Biomedical Analysis Center, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Haili
authors.initials: H
authors.lastname: Yu
authors.affiliation: Biomedical Analysis Center, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Ni
authors.affiliation: Biomedical Analysis Center, The Third Military Medical University, Chongqing 400038, China wanying.cn@gmail.com qi-jing.li@duke.edu yzhuang@duke.edu.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710; wanying.cn@gmail.com qi-jing.li@duke.edu yzhuang@duke.edu.
authors.forename: Qijing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710; wanying.cn@gmail.com qi-jing.li@duke.edu yzhuang@duke.edu.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D012641:Selection, Genetic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell
keywords: T regulatory cells; TCR repertoire; aging; lineage tracking; tolerance