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Series GSE243905 Query DataSets for GSE243905
Status Public on Apr 15, 2024
Title Single-cell TCR profiling of CSF and blood cells of PWH reveals persistent and shared infected T cell clones across tissue compartments even after ART
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The brain is a site of persistent infected cells during HIV infection. However, the dynamics of central nervous system (CNS) infection and T cell trafficking in people living with HIV (PWH) are incompletely understood. We profiled the single cell T cell repertoire and host transcriptome from paired blood and cerebrospinal fluid (CSF) from PWH and uninfected controls. We detected HIV RNA-producing cells in 8/11 (72.7 %) CSF samples and 6/11 (54.5 %) blood samples, with a higher frequency of infected single CD4 T cells in CSF than in blood. Infected CSF T cells displayed a unique transcriptional profile compared to uninfected CSF T cells. Most infected T cell clones were not shared across tissue; however, in a subset of participants we detected identical T cell clones that were infected in both CSF and blood. Longitudinally following one PWH before and at three time points after initiating ART, we found infected T cell clones that persisted after ART initiation, in both CSF and blood, including a T cell clone that expanded in the CSF several months after ART initiation. Our findings suggest that infected T cells traffic to the CNS where they undergo clonal expansion despite ART, contributing to the CNS reservoir.
Overall design Asymptomatic PWH P2 - P7 were enrolled (n = 7), and all were stable on ART (median 16 years) with suppressed plasma viral loads (< 50 copies/mL) and a median CD4 count of 503. One additional PWH was enrolled (P1) with newly diagnosed HIV and not yet on ART, and had a plasma viral load of 257,000 copies/mL. Control participants C1 - C6 were healthy volunteers recruited from the surrounding community for research sampling (n = 6) plus one hospitalized individual C1 undergoing a workup for gait instability. All control participants were confirmed HIV-negative by plasma enzyme immunoassay and screened for confounding neurological conditions. All participants consented to large-volume lumbar puncture (up to 30cc CSF removed) and blood draw for research purposes, or to donate additional CSF and blood samples collected during clinical standard-of-care procedures. Participant P1 underwent longitudinal study visits and consented to provide blood and CSF samples at HIV diagnosis/baseline and three, six, and nine months after initiating ART. The gene expression and T cell receptors of the peripheral blood and CSF samples were then measured using 5’ V(D)J 10x Genomics paired scRNA-seq and TCR-seq. Sequencing data for C1 - C3 was previously published on SRA (study accession: SRP312293, C1_BLD_RNA: SRR14076861, C1_BLD_TCR: SRR14076833, C1_CSF_RNA: SRR14076871, C1_CSF_TCR: SRR14076842, C2_BLD_RNA: SRR14076860, C2_BLD_TCR: SRR14076832, C2_CSF_RNA: SRR14076869, C2_CSF_TCR: SRR14076841, C3_BLD_RNA: SRR14076858, C3_BLD_TCR: SRR14076831, C3_CSF_RNA: SRR14076868, C3_CSF_TCR: SRR14076840).
Contributor(s) Wang M, Yoon J, Reisert H, Das B, Chiarella J, Halvas E, Pang AP, Cyktor J, Spudich S, Kluger Y, Corley MJ, Farhadian SF
Citation(s) 38587074
Submission date Sep 24, 2023
Last update date Apr 16, 2024
Contact name Shelli Farhadian
Organization name Yale University
Street address 135 College St.
City New Haven
State/province CT
ZIP/Postal code 06511
Country USA
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (82)
GSM7798067 Control C4 Blood scRNAseq (biol rep 1)
GSM7798068 Control C4 Blood scTCRseq (biol rep 1)
GSM7798069 Control C4 CSF scRNAseq
BioProject PRJNA1020551

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Supplementary file Size Download File type/resource
GSE243905_RAW.tar 1.0 Gb (http)(custom) TAR (of H5, TAR)
GSE243905_gex_aggr_filtered_feature_bc_matrix.h5 1011.2 Mb (ftp)(http) H5
GSE243905_gex_aggr_seurat.rds.gz 3.1 Gb (ftp)(http) RDS
GSE243905_gex_aggregation.csv.gz 458 b (ftp)(http) CSV
GSE243905_tcr_aggr.tar.gz 134.6 Mb (ftp)(http) TAR
SRA Run SelectorHelp
Raw data are available in SRA

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