Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq

CD4 T lymphocytes belong to diverse cellular subsets whose sensitivity or resistance to HIV-associated killing remains to be defined. Working with lymphoid cells from human tonsils, we characterized the HIV-associated depletion of various CD4 T cell subsets using mass cytometry and single-cell RNA-s...

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Main Authors: Xiaoyu Luo, Julie Frouard, Gang Zhang, Jason Neidleman, Guorui Xie, Emma Sheedy, Nadia R. Roan, Warner C. Greene
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.883420/full
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author Xiaoyu Luo
Julie Frouard
Julie Frouard
Gang Zhang
Jason Neidleman
Jason Neidleman
Guorui Xie
Guorui Xie
Emma Sheedy
Nadia R. Roan
Nadia R. Roan
Warner C. Greene
Warner C. Greene
Warner C. Greene
author_facet Xiaoyu Luo
Julie Frouard
Julie Frouard
Gang Zhang
Jason Neidleman
Jason Neidleman
Guorui Xie
Guorui Xie
Emma Sheedy
Nadia R. Roan
Nadia R. Roan
Warner C. Greene
Warner C. Greene
Warner C. Greene
author_sort Xiaoyu Luo
collection DOAJ
description CD4 T lymphocytes belong to diverse cellular subsets whose sensitivity or resistance to HIV-associated killing remains to be defined. Working with lymphoid cells from human tonsils, we characterized the HIV-associated depletion of various CD4 T cell subsets using mass cytometry and single-cell RNA-seq. CD4 T cell subsets preferentially killed by HIV are phenotypically distinct from those resistant to HIV-associated cell death, in a manner not fully accounted for by their susceptibility to productive infection. Preferentially-killed subsets express CXCR5 and CXCR4 while preferentially-infected subsets exhibit an activated and exhausted effector memory cell phenotype. Single-cell RNA-seq analysis reveals that the subsets of preferentially-killed cells express genes favoring abortive infection and pyroptosis. These studies emphasize a complex interplay between HIV and distinct tissue-based CD4 T cell subsets, and the important contribution of abortive infection and inflammatory programmed cell death to the overall depletion of CD4 T cells that accompanies untreated HIV infection.
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spelling doaj.art-b9e4cc8abcb74f8fa6ac5b6bd62165512022-12-22T03:29:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.883420883420Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seqXiaoyu Luo0Julie Frouard1Julie Frouard2Gang Zhang3Jason Neidleman4Jason Neidleman5Guorui Xie6Guorui Xie7Emma Sheedy8Nadia R. Roan9Nadia R. Roan10Warner C. Greene11Warner C. Greene12Warner C. Greene13Gladstone Institute of Virology, San Francisco, CA, United StatesGladstone Institute of Virology, San Francisco, CA, United StatesDepartment of Urology, University of California, San Francisco, San Francisco, CA, United StatesGladstone Institute of Virology, San Francisco, CA, United StatesGladstone Institute of Virology, San Francisco, CA, United StatesDepartment of Urology, University of California, San Francisco, San Francisco, CA, United StatesGladstone Institute of Virology, San Francisco, CA, United StatesDepartment of Urology, University of California, San Francisco, San Francisco, CA, United StatesGladstone Institute of Virology, San Francisco, CA, United StatesGladstone Institute of Virology, San Francisco, CA, United StatesDepartment of Urology, University of California, San Francisco, San Francisco, CA, United StatesGladstone Institute of Virology, San Francisco, CA, United StatesDepartment of Medicine, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, United StatesCD4 T lymphocytes belong to diverse cellular subsets whose sensitivity or resistance to HIV-associated killing remains to be defined. Working with lymphoid cells from human tonsils, we characterized the HIV-associated depletion of various CD4 T cell subsets using mass cytometry and single-cell RNA-seq. CD4 T cell subsets preferentially killed by HIV are phenotypically distinct from those resistant to HIV-associated cell death, in a manner not fully accounted for by their susceptibility to productive infection. Preferentially-killed subsets express CXCR5 and CXCR4 while preferentially-infected subsets exhibit an activated and exhausted effector memory cell phenotype. Single-cell RNA-seq analysis reveals that the subsets of preferentially-killed cells express genes favoring abortive infection and pyroptosis. These studies emphasize a complex interplay between HIV and distinct tissue-based CD4 T cell subsets, and the important contribution of abortive infection and inflammatory programmed cell death to the overall depletion of CD4 T cells that accompanies untreated HIV infection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.883420/fullhuman immunodeficiency virus (HIV)cell deathapoptosispyroptosislymphoid tissuesmass cytometry
spellingShingle Xiaoyu Luo
Julie Frouard
Julie Frouard
Gang Zhang
Jason Neidleman
Jason Neidleman
Guorui Xie
Guorui Xie
Emma Sheedy
Nadia R. Roan
Nadia R. Roan
Warner C. Greene
Warner C. Greene
Warner C. Greene
Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq
Frontiers in Immunology
human immunodeficiency virus (HIV)
cell death
apoptosis
pyroptosis
lymphoid tissues
mass cytometry
title Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq
title_full Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq
title_fullStr Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq
title_full_unstemmed Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq
title_short Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq
title_sort subsets of tissue cd4 t cells display different susceptibilities to hiv infection and death analysis by cytof and single cell rna seq
topic human immunodeficiency virus (HIV)
cell death
apoptosis
pyroptosis
lymphoid tissues
mass cytometry
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.883420/full
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