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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Frontiers Media S.A.
2022-06-01
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Series: | Frontiers in Immunology |
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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. |
first_indexed | 2024-04-12T14:16:53Z |
format | Article |
id | doaj.art-b9e4cc8abcb74f8fa6ac5b6bd6216551 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-12T14:16:53Z |
publishDate | 2022-06-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
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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