Work

Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes

Year: 2023

Type: article

Abstract: IL-7 is a homeostatic cytokine critical in development and maintenance of T lymphocytes. We employed a novel dose-escalation regimen in rhesus macaques using glycosylated IL-7. In addition to systemic proliferation and survival of T cells, IL-7 triggered several chemokines, including CXCL13. This led to a remarkable increase of B cells in the lymph nodes (LNs), proliferation of germinal center follicular T helper cells and elevated IL-21 levels suggesting an increase in follicle activity. Transcriptomics analysis suggested an induction of IRF-7 and Flt3L linked to increased frequency of circulating plasmacytoid dendritic cells (pDCs) upon IL-7 treatment. These pDCs expressed higher levels of CCR7 and subsequent homing to the LNs. Increased pDCs was associated with an upregulation of a type-1 interferon gene signature and increased production of IFN-α2a upon TLR stimulation. IL-7 treatment leads to systemic effects involving both lymphoid and myeloid compartments that can contribute to the outcome of the therapy. Funding Information: This work was supported in part by funding from the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research to GNP and BKF and with Federal Funds from the National Cancer Institute, National Institutes of Health, under contracts number 75N91019D00024 and HHSN261200800001E. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The macaque studies were conducted in compliance with all applicable state and federal regulations and were approved by BIOQUAL’s Institutional Animal Care and Use Committee (IACUC).

Source: iScience

DOI: 10.1016/j.isci.2023.105929