The influence of three-dimensional structure on naïve T cell homeostasis and aging

Simon Lambert; Wenqiang Cao; Huimin Zhang; Alex Colville; Jie Yu Liu; Cornelia M. Weyand; Jorg J. Goronzy; Claire E. Gustafson

doi:10.3389/fragi.2022.1045648

The influence of three-dimensional structure on naïve T cell homeostasis and aging

Simon Lambert, Wenqiang Cao, Huimin Zhang, Alex Colville, Jie Yu Liu, Cornelia M. Weyand, Jorg J. Goronzy, Claire E. Gustafson

Immunology

Research output: Contribution to journal › Article › peer-review

Abstract

A breakdown in cellular homeostasis is thought to drive naïve T cell aging, however the link between naïve T cell homeostasis and aging in humans is poorly understood. To better address this, we developed a lymphoid organoid system that maintains resting naïve T cells for more than 2 weeks, in conjunction with high CD45RA expression. Deep phenotypic characterization of naïve T cells across age identified reduced CD45RA density as a hallmark of aging. A conversion from CD45RA^high naive cells to a CD45RA^low phenotype was reproduced within our organoid system by structural breakdown, but not by stromal cell aging or reduced lymphocyte density, and mediated by alternative CD45 splicing. Together, these data suggest that external influences within the lymph node microenvironment may cause phenotypic conversion of naïve T cells in older adults.

Original language	English (US)
Article number	1045648
Journal	Frontiers in Aging
Volume	3
DOIs	https://doi.org/10.3389/fragi.2022.1045648
State	Published - 2022

Keywords

alternative splicing
homeostasis
immune age
naïve T cells
organoids
secondary lymphoid tissues

ASJC Scopus subject areas

Aging
Genetics
Molecular Biology
Physiology

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10.3389/fragi.2022.1045648

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title = "The influence of three-dimensional structure on na{\"i}ve T cell homeostasis and aging",

abstract = "A breakdown in cellular homeostasis is thought to drive na{\"i}ve T cell aging, however the link between na{\"i}ve T cell homeostasis and aging in humans is poorly understood. To better address this, we developed a lymphoid organoid system that maintains resting na{\"i}ve T cells for more than 2 weeks, in conjunction with high CD45RA expression. Deep phenotypic characterization of na{\"i}ve T cells across age identified reduced CD45RA density as a hallmark of aging. A conversion from CD45RAhigh naive cells to a CD45RAlow phenotype was reproduced within our organoid system by structural breakdown, but not by stromal cell aging or reduced lymphocyte density, and mediated by alternative CD45 splicing. Together, these data suggest that external influences within the lymph node microenvironment may cause phenotypic conversion of na{\"i}ve T cells in older adults.",

keywords = "alternative splicing, homeostasis, immune age, na{\"i}ve T cells, organoids, secondary lymphoid tissues",

author = "Simon Lambert and Wenqiang Cao and Huimin Zhang and Alex Colville and Liu, {Jie Yu} and Weyand, {Cornelia M.} and Goronzy, {Jorg J.} and Gustafson, {Claire E.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 Lambert, Cao, Zhang, Colville, Liu, Weyand, Goronzy and Gustafson.",

year = "2022",

doi = "10.3389/fragi.2022.1045648",

language = "English (US)",

volume = "3",

journal = "Frontiers in Aging",

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T1 - The influence of three-dimensional structure on naïve T cell homeostasis and aging

AU - Lambert, Simon

AU - Cao, Wenqiang

AU - Zhang, Huimin

AU - Colville, Alex

AU - Liu, Jie Yu

AU - Weyand, Cornelia M.

AU - Goronzy, Jorg J.

AU - Gustafson, Claire E.

PY - 2022

Y1 - 2022

N2 - A breakdown in cellular homeostasis is thought to drive naïve T cell aging, however the link between naïve T cell homeostasis and aging in humans is poorly understood. To better address this, we developed a lymphoid organoid system that maintains resting naïve T cells for more than 2 weeks, in conjunction with high CD45RA expression. Deep phenotypic characterization of naïve T cells across age identified reduced CD45RA density as a hallmark of aging. A conversion from CD45RAhigh naive cells to a CD45RAlow phenotype was reproduced within our organoid system by structural breakdown, but not by stromal cell aging or reduced lymphocyte density, and mediated by alternative CD45 splicing. Together, these data suggest that external influences within the lymph node microenvironment may cause phenotypic conversion of naïve T cells in older adults.

AB - A breakdown in cellular homeostasis is thought to drive naïve T cell aging, however the link between naïve T cell homeostasis and aging in humans is poorly understood. To better address this, we developed a lymphoid organoid system that maintains resting naïve T cells for more than 2 weeks, in conjunction with high CD45RA expression. Deep phenotypic characterization of naïve T cells across age identified reduced CD45RA density as a hallmark of aging. A conversion from CD45RAhigh naive cells to a CD45RAlow phenotype was reproduced within our organoid system by structural breakdown, but not by stromal cell aging or reduced lymphocyte density, and mediated by alternative CD45 splicing. Together, these data suggest that external influences within the lymph node microenvironment may cause phenotypic conversion of naïve T cells in older adults.

KW - alternative splicing

KW - homeostasis

KW - immune age

KW - naïve T cells

KW - organoids

KW - secondary lymphoid tissues

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JO - Frontiers in Aging

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The influence of three-dimensional structure on naïve T cell homeostasis and aging

Abstract

Keywords

ASJC Scopus subject areas

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