期刊
IMMUNITY
卷 55, 期 6, 页码 1013-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2022.03.004
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类别
资金
- Yale Top Scholar, Rudolf J. Anderson Fellowship
- NIH REACH Martin Delaney Collaboratory [UM1 AI164565]
- NIH BEAT-HIV Martin Delaney Collaboratory [UM1 AI126620]
- American Foundation for AIDS Research (amfAR) [110029-67-RGRL]
- Robert I. Jacobs Fund of The Philadelphia Foundation
- Yale Gruber Fellowship
- Yale Center for Genome Analysis-10X Genomics Pilot Award
- NIH [R01 AI141009, R61/R33 DA047037, R37 AI147868, R01 DA051906, R01AI145164, UM1 DA051410, U01 DA053628, CHEETAH P50 AI150464, T32 AI055403, R01 DA032106, R01 DA040532]
Understanding the driving factors and markers of clonally expanding HIV-1-infected CD4(+) T cells is crucial for the eradication of HIV-1. Utilizing single-cell ECCITE-seq technology, researchers tracked the dynamics of clonal expansion in longitudinally archived samples from HIV-1-infected individuals and uninfected individuals. The study revealed that persistent antigen and TNF responses shaped T cell clonal expansion, even in the presence of antiretroviral therapy. Additionally, HIV-1-infected cytotoxic CD4(+) T cell clones persisted and were enriched in cytotoxic effector memory Th1 cells.
Understanding the drivers and markers of clonally expanding HIV-1-infected CD4(+) T cells is essential for HIV-1 eradication. We used single-cell ECCITE-seq, which captures surface protein expression, cellular transcriptome, HIV-1 RNA, and TCR sequences within the same single cell to track clonal expansion dynamics in longitudinally archived samples from six HIV-1-infected individuals (during viremia and after suppressive antiretroviral therapy) and two uninfected individuals, in unstimulated conditions and after CMV and HIV-1 antigen stimulation. Despite antiretroviral therapy, persistent antigen and TNF responses shaped T cell clonal expansion. HIV-1 resided in Th1-polarized, antigen-responding T cells expressing BCL2 and SERPINB9 that may resist cell death. HIV-1 RNA(+) T cell clones were larger in clone size, established during viremia, persistent after viral suppression, and enriched in GZMB(+) cytotoxic effector memory Th1 cells. Targeting HIV-1-infected cytotoxic CD4(+) T cells and drivers of clonal expansion provides another direction for HIV-1 eradication.
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