IL-15 induces type 1 and type 2 CD4+ and CD8+ T cells proliferation but is unable to drive cytokine production in the absence of TCR activation or IL-12 / IL-4 stimulation in vitro

Abstract

Interleukin 15 (IL-15) is a pleiotropic cytokine produced principally by monocytes and affects both innate and acquired immunity. It has been shown that IL-15 is essential for the proliferation and maintenance of CD8+ memory cells but has little or no effect on naive CD8+ cells or CD4+ T cells. We report here, using an in vitro culture system of antigen-specific OVA TCR transgenic T cells as well as normal mouse T cell activated with anti-CD3 antibody that IL-15, at high concentrations, induced proliferation of both naive and memory CD4+ and CD8+ cells. IL-15 also enhanced the differentiation of type 1 (IFN-gamma-producing) and type 2 (IL-5-producing) CD4+ and CD8+ T cells under IL-12 and IL-4 driving conditions, respectively. However, IL-15 alone was not efficient in stimulating cytokine production of these cells in the absence of T cell subset driving cytokines (IL-12 or IL-4) and / or simultaneous TCR activation. Together, these results demonstrate that IL-15, at high dose, is a pan-T cell growth factor. The apparent requirement of IL-15 for the maintenance of memory CD8+ cell in vivo may reflect the exceptionally restricted nature of this subpopulation of cells for IL-15. The inability of IL-15 alone to stimulate cytokine synthesis also suggests that IL-15 on its own does not drive antigen-specific T cells to exhaustion. The levels of these cells are maintained by IL-15 and they are only mobilized to carry out effector functions when subsequently confronted with specific pathogens.