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

ABSTRACT: 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.

SUBMITTER: Luo X

PROVIDER: S-EPMC9245423 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Luo Xiaoyu X Frouard Julie J Zhang Gang G Neidleman Jason J Xie Guorui G Sheedy Emma E Roan Nadia R NR Greene Warner C WC

Frontiers in immunology 20220616

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 produc ...[more]

PMID: 35784348

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Project description:IntroductionAfter mild COVID-19 that does not require hospitalization, some individuals develop persistent symptoms that may worsen over time, producing a multisystemic condition termed Post-COVID condition (PCC). Among other disorders, PCC is characterized by persistent changes in the immune system that may not be solved several months after COVID-19 diagnosis.MethodsPeople with PCC were recruited to determine the distribution and functionality of CD4+ T helper (Th) subsets in comparison with individuals with mild, severe, and critical presentations of acute COVID-19 to evaluate their contribution as risk or protective factors for PCC.ResultsPeople with PCC showed low levels of Th1 cells, similar to individuals with severe and critical COVID-19, although these cells presented a higher capacity to express IFNγ in response to stimulation. Th2/Th1 correlation was negative in individuals with acute forms of COVID-19, but there was no significant Th2/Th1 correlation in people with PCC. Th2 cells from people with PCC presented high capacity to express IL-4 and IL-13, which are related to low ventilation and death associated with COVID-19. Levels of proinflammatory Th9 and Th17 subsets were significantly higher in people with PCC in comparison with acute COVID-19, being Th1/Th9 correlation negative in these individuals, which probably contributed to a more pro-inflammatory than antiviral scenario. Th17 cells from approximately 50% of individuals with PCC had no capacity to express IL-17A and IL-22, similar to individuals with critical COVID-19, which would prevent clearing extracellular pathogens. Th2/Th17 correlation was positive in people with PCC, which in the absence of negative Th1/Th2 correlation could also contribute to the proinflammatory state. Finally, Th22 cells from most individuals with PCC had no capacity to express IL-13 or IL-22, which could increase tendency to reinfections due to impaired epithelial regeneration.DiscussionPeople with PCC showed skewed polarization of CD4+ Th subsets with altered functionality that was more similar to individuals with severe and critical presentations of acute COVID-19 than to people who fully recovered from mild disease. New strategies aimed at reprogramming the immune response and redirecting CD4+ Th cell polarization may be necessary to reduce the proinflammatory environment characteristic of PCC.

Dataset Information

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

Publications

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

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