Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes
Summary: 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 cells and triggered several chemokines and cytokines. Induction of CXCL13 in lymph node...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000068 |
| _version_ | 1797903407958196224 |
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| author | Hrishikesh Pandit Antonio Valentin Matthew Angel Claire Deleage Cristina Bergamaschi Jenifer Bear Raymond Sowder Barbara K. Felber George N. Pavlakis |
| author_facet | Hrishikesh Pandit Antonio Valentin Matthew Angel Claire Deleage Cristina Bergamaschi Jenifer Bear Raymond Sowder Barbara K. Felber George N. Pavlakis |
| author_sort | Hrishikesh Pandit |
| collection | DOAJ |
| description | Summary: 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 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-α2a 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. |
| first_indexed | 2024-04-10T09:32:24Z |
| format | Article |
| id | doaj.art-d3af30d85067445a9fb29a6876052178 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:32:24Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d3af30d85067445a9fb29a68760521782023-02-19T04:26:35ZengElsevieriScience2589-00422023-02-01262105929Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodesHrishikesh Pandit0Antonio Valentin1Matthew Angel2Claire Deleage3Cristina Bergamaschi4Jenifer Bear5Raymond Sowder6Barbara K. Felber7George N. Pavlakis8Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAVaccine 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, USAAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA; Corresponding authorSummary: 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 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-α2a 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.http://www.sciencedirect.com/science/article/pii/S2589004223000068Immune systemImmune responseComponents of the immune system |
| spellingShingle | Hrishikesh Pandit Antonio Valentin Matthew Angel Claire Deleage Cristina Bergamaschi Jenifer Bear Raymond Sowder Barbara K. Felber George N. Pavlakis Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes iScience Immune system Immune response Components of the immune system |
| title | Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes |
| title_full | Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes |
| title_fullStr | Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes |
| title_full_unstemmed | Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes |
| title_short | Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes |
| title_sort | step dose il 7 treatment promotes systemic expansion of t cells and alters immune cell landscape in blood and lymph nodes |
| topic | Immune system Immune response Components of the immune system |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223000068 |
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