Phenotypic changes induced by IL-12 priming regulate effector and memory CD8 T cell differentiation

Abstract

In addition to TCR and co-stimulatory signals, inflammatory cytokines such as IL-12 provide important signals for differentiation and survival of activated CD8 T cells. In the present study, to investigate the mechanisms by which IL-12 priming contributes to activation and enhanced survival of CD8 T cells, we searched the differentially regulated genes and markers by IL-12 during antigenic stimulation. Here, we show that IL-12 priming results in the increased subpopulation of CD127(hi) cells, which differentiates into long-lived memory cells. We also found that IL-12 priming induces IL-10 expression from activated CD8 T cells, which is distinct from CD127 up-regulation. Direct IL-10 priming of CD8 T cells results in the significant increase of effector and memory CD8 T cell population after adoptive transfer, and this priming effect is closely associated with less susceptibility to apoptosis. Although IL-10 is known as a cytokine with anti-inflammatory and immunosuppressive properties, our results have shown that IL-10 has a direct and positive effect on the survival of CD8 T cells. Together, we suggest that IL-10-dependent and independent effects of IL-12 play important roles in regulating differentiation and survival of activated CD8 T cells into effector and memory cells.