Step-dose IL-7 treatment promotes systemic expansion of T cells and alters immune cell landscape in blood and lymph nodes
Hrishikesh Pandit, Antonio Valentin, Matthew Angel, Claire Deléage, Cristina Bergamaschi, Jenifer Bear, Raymond C. Sowder, Barbara K. Felber, George N. Pavlakis
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 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.