Out-sourcing for Trans-presentation: Assessing T Cell Intrinsic and Extrinsic IL-15 Expression with Il15 Gene Reporter Mice

Abstract

IL-15 is a cytokine of the common γ-chain family that is critical for natural killer (NK), invariant natural killer T (iNKT), and CD8 memory T cell development and homeostasis. The role of IL-15 in regulating effector T cell subsets, however, remains incompletely understood. IL-15 is mostly expressed by stromal cells, myeloid cells, and dendritic cells (DCs). Whether T cells themselves can express IL-15, and if so, whether such T cell-derived IL-15 could play an autocrine role in T cells are interesting questions that were previously addressed but answered with mixed results. Recently, three independent studies described the generation of IL-15 reporter mice which facilitated the identification of IL-15-producing cells and helped to clarify the role of IL-15 both in vitro and in vivo. Here, we review the findings of these studies and place them in context of recent reports that examined T cell-intrinsic IL-15 expression during CD4 effector T cell differentiation.

Keywords: Cytokine receptor; Cytokine signaling; Inflammation; Th17 cells.

Figure 1

IL-15 expression and trans-presentation. (A) IL-15 is mostly expressed by non-lymphoid cells, such as stromal cells, myeloid cells, and DCs. T cells, on the other hand, are an unlikely source of IL-15. (B) IL-15 is trans-presented by IL-15Rα and signals through the IL-2Rβ/γc heterodimeric cytokine receptor that is expressed on T cells. (C) IL-15 signaling in T cells depend on IL-15 that is expressed and presented in trans, because effector T cells do not express IL-15 and cannot signal in cis.