Enhancement of proliferation and downregulation of TRAIL expression on CD8+ T cells by IL-21.

Mounting evidence indicates that the cytokine IL-21 can significantly enhance the survival of CD8(+) T lymphocytes. Given that CD4(+) T lymphocytes constitute the main cellular source for IL-21 in vivo, it is tempting to speculate a direct role in mediating the "help" provided by these CD4(+) T cells to the CD8 response. A new report in this issue of the European Journal of Immunology advances this notion by showing that CD8(+) T cells lacking the IL-21 receptor phenocopy those primed in the absence of CD4(+) T cells (the so-called "helpless" CD8(+) T cells) in their induction of the pro-apoptotic factor TRAIL. This finding helps to define the role of IL-21 in the CD8 response, and raises new questions relevant for achieving a broader understanding of this multifunctional cytokine.