English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

IL-15 is an important cytokine involved in the survival and function of CD8(+) T cells and NK cells. IL-15 can be presented by IL-15Ralpha (IL-15RA) to bind with the shared IL-2/IL-15Rbeta and common gamma-chains, which activate signaling pathways on NK cells and CD8(+) T cells. In the present study, we characterized the function of trans-presented IL-15 on NK cells and CD8(+) T cells using TC-1 tumor cells transduced with a retrovirus encoding IL-15 linked to IL-15RA (IL-15/IL-15RA). We demonstrated that the expression of IL-15/IL-15RA on TC-1 cells led to increased percentages of tumor-infiltrating NK cells, NKT cells, and CD8(+) T cells, resulting in the inhibition of tumor growth in challenged mice. Additionally, in vivo Ab depletion experiments demonstrated that NK1.1(+) cells and CD8(+) T cells were important in this inhibition of tumor growth. Furthermore, this accumulation of immune cells and inhibition of tumor growth was abolished by a single amino acid mutation in the common gamma-chain binding site on IL-15. We also observed that IL-15/IL-15RA-transduced TC-1 cells led to the activation of STAT5 in NK and CD8(+) T cells in trans, which was abolished in the mutated IL-15/IL-15RA-transduced TC-1 cells. Taken together, our data suggest that common gamma-chain binding-dependent activation of the shared IL-15/IL-2Rbeta/common gamma signaling pathway may play an important role in the activation of NK cells and CD8(+) T cells, resulting in IL-15/IL-15RA trans-presentation-mediated inhibition of tumor growth.

Inhibition of Tumor Growth by NK1.1+ Cells and CD8+ T Cells Activated by IL-15 through Receptor β/Common γ Signaling in trans