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A single administration of hIL-7-hyFc induces long-lasting T-cell expansion with maintained effector functions

 Sojeong Kim  ;  Sang Won Lee  ;  June-Young Koh  ;  Donghoon Choi  ;  Minkyu Heo  ;  Jae-Yong Chung  ;  Byung Ha Lee  ;  Se Hwan Yang  ;  Young Chul Sung  ;  Howard Lee  ;  Eui-Cheol Shin  ;  Su-Hyung Park 
 BLOOD ADVANCES, Vol.6(23) : 6093-6107, 2022-12 
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Adult ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cell Proliferation ; Humans ; Interleukin-7* / pharmacology ; T-Lymphocyte Subsets*
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 (Tregs) did not expand. Among CD8+ and CD4+ T cells, all T-cell subsets (TN, TEM, TCM, TEMRA, and TSCM) increased for 56 days. The T-cell receptor repertoire diversity of naive CD8+ and CD4+ T cells was increased by hIL-7-hyFc, whereas the memory T-cell subsets did not differ between day 56 and day 0. 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 Tregs, 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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, So Jeong(김소정)
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