IL-21 and T Cell Differentiation: Consider the Context

Accumulating studies demonstrate that IL-21 modulates the differentiation of various CD4 and CD8 T cell subsets and provide insights into the underlying cellular and molecular processes that are influenced by this cytokine. Intriguingly, the effects of IL-21 on T cells can be complex and vary depending on the experimental system used. We review our current understanding of the roles of IL-21 in the generation of phenotypically distinct CD4 and CD8 T cell populations and discuss the potential environmental cues, cellular factors, and molecular mediators that impact the actions of IL-21. We propose that IL-21 acts in a context-dependent manner to accentuate T cell subset development.