Overexpression of IL‐21 promotes massive CD8+ memory T cell accumulation

EL Allard, MP Hardy, J Leignadier… - European journal of …, 2007 - Wiley Online Library
EL Allard, MP Hardy, J Leignadier, M Marquis, J Rooney, D Lehoux, N Labrecque
European journal of immunology, 2007Wiley Online Library
The ability of IL‐21 to promote in vitro T cell survival led us to investigate its biological
activity in vivo. We report that overexpression of IL‐21 in transgenic mice drives CD8+
memory T cell accumulation with a concomitant reduction in naive T cell numbers. These
memory T cells are functional, given their ability to rapidly produce IFN‐γ and proliferate
following stimulation. Since the homeostasis of naive and memory T cells is controlled by
cytokines, we evaluated whether IL‐21 influences cytokine receptor expression. We show …
Abstract
The ability of IL‐21 to promote in vitro T cell survival led us to investigate its biological activity in vivo. We report that overexpression of IL‐21 in transgenic mice drives CD8+ memory T cell accumulation with a concomitant reduction in naive T cell numbers. These memory T cells are functional, given their ability to rapidly produce IFN‐γ and proliferate following stimulation. Since the homeostasis of naive and memory T cells is controlled by cytokines, we evaluated whether IL‐21 influences cytokine receptor expression. We show that IL‐21 inhibits IL‐7R expression on naive T cells in vitro, suggesting impaired IL‐7‐mediated naive T cell survival in IL‐21‐transgenic mice. In contrast, IL‐7R expression on CD4+ memory T cells is not affected, allowing their IL‐7‐dependent survival in IL‐21‐transgenic mice. Although IL‐21 decreases IL‐7R expression on CD8+ memory T cells, this has no impact on their survival since their maintenance in the T cell pool is IL‐7‐independent. Rather, we demonstrate that CD8+ memory T cells are receptive to IL‐21 survival signals allowing for their accumulation in IL‐21‐transgenic mice. This study identifies new roles for IL‐21 in T cell homeostasis and in the regulation of T cell responses to cytokines.
Wiley Online Library