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

  1. Author:
    Pandit,Hrishikesh
    Valentin, Antonio
    Angel, Matthew
    Deleage,Claire
    Bergamaschi, Cristina
    Bear,Jenifer
    Sowder, Raymond
    Felber,Barbara
    Pavlakis,George

  2. Author Address

    Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA., Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Center for Cancer Research Collaborative Bioinformatics Resource, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA., Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.,
    1. Year: 2023
    2. Date: Feb 17
    3. Epub Date: 2023 01 05
  2. Journal: iScience
    1. 26
    2. 2
    3. Pages: 105929
  4. Type of Article: Article
  5. Article Number: 105929
  1. Abstract:

    We employed a dose-escalation regimen in rhesus macaques to deliver glycosylated IL-7, a cytokine critical for development and maintenance of T lymphocytes. IL-7 increased proliferation and survival of T 160;cells and triggered several chemokines and cytokines. Induction of CXCL13 in lymph nodes (LNs) led to a remarkable increase of B cells in the LNs, proliferation of germinal center follicular T helper cells and elevated IL-21 levels suggesting an increase in follicle activity. Transcriptomics analysis showed induction of IRF-7 and Flt3L, which was linked to increased frequency of circulating plasmacytoid dendritic cells (pDCs) on IL-7 treatment. These pDCs expressed higher levels of CCR7, homed to LNs, and were associated with upregulation of type-1 interferon gene signature and increased production of IFN-a2a on TLR stimulation. Superior effects and dose-sparing advantage was observed by the step-dose regimen. Thus, IL-7 treatment leads to systemic effects involving both lymphoid and myeloid compartments.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.isci.2023.105929
  3. PMID: 36685042
  4. PMCID: PMC9852696
  5. PII : S2589-0042(23)00006-8

Library Notes

  1. Fiscal Year: FY2022-2023
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