Tc17 Cells in Immunity and Systemic Autoimmunity

Tc17 cells-a subset of CD8(+)T cells-have recently been identified that are characterized by the production of interleukin (IL)-17. Cytokines IL-6 and transforming growth factor-beta 1 (TGF-β1) and transcription factors signaling transducers and activators of transcription (STAT)3, retinoic acid receptor-related orphan nuclear receptor gamma (RORγt), and interferon regulatory factor (IRF)4 are necessary for differentiation of Tc17 cells, controlling expression of molecules essential for Tc17 cell trafficking and function. Current human researches have determined the significance of CD161 expression as either a marker of Tc17 cells or as an effector and regulator of Tc17 cell function. Noncytotoxic Tc17 cells possess a high plasticity to convert into IFN-γ producing cells, which exhibit strong cytotoxic activity. The importance of in vivo plasticity of Tc17 cells for the induction of autoimmune diseases has been demonstrated and Tc17 cells potentially represent novel therapeutic targets in autoimmune diseases. The involvement of interleukin (IL)-17-producing CD8(+)T cells (Tc17) in various conditions, such as infection, cancer, and autoimmune inflammation, has been documented in both humans and mice; however, Tc17 cells have received only marginal attention. Here, we provide an overview of the cytokines and chemokines that characterize the murine and human Tc17 cells. Moreover, we discuss signaling pathways, molecular interactions, and transcriptional events that contribute to Tc17 differentiation and acquisition of effector functions. Also considered is the basis of Tc17 cell plasticity toward the Tc1 lineage, and we suggest that in vivo plasticity of Tc17 cells may be a key feature of Tc17 cell biology in autoimmune diseases. Furthermore, current human researches have revealed that Tc17 cells are different than that in mice because all of them express CD161 and exclusively originate from CD161 precursors present in umbilical cord blood. Finally, we focus on the recent evidence for long-lived Tc17 memory cell populations in mouse models and humans, and their functional roles in mediating disease memory. Hopefully, the information obtained will benefit for developing novel therapeutic strategies.