IL-15 is a n important cytokine involved in the survival and function of CD8+ T cells and NK cells. IL-15 can be presented by IL-15Rα(IL-15RA) to bind with the shared IL-2/IL-15Rβ and common γ-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 γ-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 γ-chain binding-dependent activation of the shared IL-15/IL-2Rβ/common γ 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.
ASJC Scopus subject areas
- Immunology and Allergy