CpG and Interleukin-15 Synergize to Enhance IFN-γ Production by Activated CD8+ T Cells

Abstract EN

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8+ T cells.

Paradoxically, we previously reported that IL-15 could enhance CD8+ T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8+ T cells.

To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG.

Expectedly, CpG enhanced the production of IFN-γ by CD8+ T cells polyclonally activated with anti-CD3.

However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-γ production.

The effect of CpG and IL-15 was also evident with CD8+ T cells recovered from mice infected with the parasite Trypanosoma cruzi (T.

cruzi) and restimulated with antigen.

The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8+ T cells and CD4+CD25+ regulatory T cells.

Although IFN-γ was not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8+ T cells required expression of the IFN-γ-inducible transcription factor T-bet.

These data have important implications for development of vaccines and design of therapies to boost CD8+ T-cell responses to infectious agents and tumors.