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Series GSE214137 Query DataSets for GSE214137
Status Public on Oct 02, 2022
Title A single administration of hIL-7-hyFc induces long-lasting T-cell expansion with maintained effector functions and TCR repertoire diversity
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Other
Summary Interleukin-7 (IL-7) is an essential cytokine for T-cell homeostatic proliferation and maintenance. Clinical studies have shown the potential benefits of IL-7 therapy in various diseases associated with lymphopenia. However, the kinetics of the T-cell response to a single administration of IL-7 in humans have not been fully elucidated. Here, we investigated the effects of Fc-fused long-acting recombinant human IL-7 (hIL-7-hyFc, efineptakin alfa) on lymphocytes in healthy adults after a single subcutaneous or intramuscular administration. Administration of hIL-7-hyFc increased the CD8+ and CD4+ T-cell numbers up to 2.5-fold, with corresponding upregulation of Ki-67 and Bcl-2 expression, peaking at day 3 or 7. Regulatory T cells did not expand. Among CD8+ and CD4+ T cells, all T-cell subsets (TN, TEM, TCM, TEMRA, and TSCM) increased for 56 days. The TCR repertoire diversity of naïve CD8+ and CD4+ T cells was increased by hIL-7-hyFc, while the memory T-cell subsets did not differ between D56 and D0. Transcriptomic analysis revealed that hIL-7-hyFc induced robust T-cell expansion without changes in gene expression profiles associated with T-cell functions or genes related to T-cell exhaustion, senescence, and anergy. The effector functions of antigen-specific CD8+ T cells were preserved after hIL-7-hyFc administration. Our results suggest that hIL-7-hyFc administration induced a sustained increase in the numbers of CD8+ and CD4+ T cells, but not regulatory T cells, without qualitative changes. These results support the potential of hIL-7-hyFc as a treatment for patients with compromised T-cell immunity or as a vaccine adjuvant.
 
Overall design RNA-seq using RNA of isolated naïve and memory CD4 and CD8 T cells from PBMCs of healthy donors before (D0) and after a single-dose administration of hIL-7-hyFc (D7 and Post (D21-56)), and IR-seq using RNA of isolated naïve and memory CD4 and CD8 T cells from PBMCs of healthy donors before (D0) and after a single-dose administration of hIL-7-hyFc (Post)
 
Contributor(s) Kim S, Lee SW, Koh J, Choi D, Heo M, Chung J, Lee BH, Yang SH, Sung YC, Lee H, Shin E, Park S
Citation(s) 36206199
Submission date Sep 25, 2022
Last update date Jan 08, 2023
Contact name Sojeong Kim
E-mail(s) sjkim0330@yuhs.ac
Phone 821043371607
Organization name Korea Advanced Institute of Science and Technology
Street address KAIST, 291 Daehak-ro, Yuseong-gu
City Daejeon
ZIP/Postal code ASI|KR|KS015|DAEJEON
Country South Korea
 
Platforms (3)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21697 NextSeq 550 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (132)
GSM6599911 S203_D0_CD8_ME RNAseq
GSM6599912 S203_D0_CD8_NA RNAseq
GSM6599913 S203_Post_CD8_NA RNAseq
Relations
BioProject PRJNA884106

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE214137_Memory_read_count_duple_ex.txt.gz 1.1 Mb (ftp)(http) TXT
GSE214137_Naive_read_count_duple_ex.txt.gz 1.1 Mb (ftp)(http) TXT
GSE214137_RAW.tar 308.3 Mb (http)(custom) TAR (of TXT)
GSE214137_gene.expression_CD4.txt.gz 8.7 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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