title: Longterm maintenance of human naive T cells throughin situhomeostasis in lymphoid tissue sites.
abstract: Naïve T cells develop in the thymus and coordinate immune responses to new antigens; however, mechanisms for their long-term persistence over the human lifespan remain undefined. Here, we investigated human naïve T cell development and maintenance in primary and secondary lymphoid tissues obtained from individual organ donors aged 3 months-73 years. In the thymus, the frequency of double-positive thymocytes declined sharply in donors over age 40 coincident with reduced recent thymic emigrants (RTE) in lymphoid tissues, while naïve T cells were functionally maintained predominantly in lymph nodes (LN). Analysis of TCR clonal distribution by CDR3 sequencing of naïve CD4+and CD8+T cells in spleen and LNs reveal site-specific clonal expansions of naïve T cells from individuals >40 years of age with minimal clonal overlap between lymphoid tissues. We also identified biased naïve T cell clonal distribution within specific lymph nodes based on VJ usage. Together these results suggest prolonged maintenance of naïve T cells throughin situhomeostasis and retention in lymphoid tissue.
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Joseph J C
authors.initials: JJ
authors.lastname: Thome
authors.affiliation: Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Grinshpun
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Brahma V
authors.initials: BV
authors.lastname: Kumar
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Masa
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohmura
authors.affiliation: LiveOnNY, New York, NY 10001, USA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Lerner
authors.affiliation: Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.affiliation: Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Farber