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Multiple genetic programs contribute to CD4 T cell memory differentiation and longevity by maintaining T cell quiescence.


ABSTRACT: While memory T-cells represent a hallmark of adaptive immunity, little is known about the genetic mechanisms regulating the longevity of memory CD4 T cells. Here, we studied the dynamics of gene expression in antigen specific CD4 T cells during infection, memory differentiation, and long-term survival up to nearly a year in mice. We observed that differentiation into long lived memory cells is associated with increased expression of genes inhibiting cell proliferation and apoptosis as well as genes promoting DNA repair response, lipid metabolism, and insulin resistance. We identified several transmembrane proteins in long-lived murine memory CD4 T cells, which co-localized exclusively within the responding antigen-specific memory CD4 T cells in human. The unique gene signatures of long-lived memory CD4 T cells, along with the new markers that we have defined, will enable a deeper understanding of memory CD4 T cell biology and allow for designing novel vaccines and therapeutics.

SUBMITTER: Song N 

PROVIDER: S-EPMC7737224 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Multiple genetic programs contribute to CD4 T cell memory differentiation and longevity by maintaining T cell quiescence.

Song Nianbin N   Sengupta Srona S   Khoruzhenko Stanislav S   Welsh Robin A RA   Kim AeRyon A   Kumar Mithra R MR   Sønder Søren Ulrik SU   Sidhom John-William JW   Zhang Hao H   Jie Chunfa C   Siliciano Robert F RF   Sadegh-Nasseri Scheherazade S  

Cellular immunology 20200905


While memory T-cells represent a hallmark of adaptive immunity, little is known about the genetic mechanisms regulating the longevity of memory CD4 T cells. Here, we studied the dynamics of gene expression in antigen specific CD4 T cells during infection, memory differentiation, and long-term survival up to nearly a year in mice. We observed that differentiation into long lived memory cells is associated with increased expression of genes inhibiting cell proliferation and apoptosis as well as ge  ...[more]

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