IL-21 Limits Peripheral Lymphocyte Numbers through T Cell Homeostatic Mechanisms

BACKGROUND: IL-21, a member of the common γ-chain utilizing family of cytokines, participates in immune and inflammatory processes. In addition, the cytokine has been linked to autoimmunity in humans and rodents. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the mechanism whereby IL-21 affects the immune system, we investigated its role in T cell homeostasis and autoimmunity in both non-autoimmune C57BL/6 and autoimmune NOD mice. Our data indicate that IL-21R knockout C57BL/6 and NOD mice show increased size of their lymphocyte population and decreased homeostatic proliferation. In addition, our experimental results demonstrate that IL-21 inhibits T cell survival. These data suggest that IL-21 acts to limit the size of the T cell pool. Furthermore, our data suggest IL-21 may contribute to the development of autoimmunity. CONCLUSIONS/SIGNIFICANCE: Taken together, our results suggest that IL-21 plays a global role in regulating T cell homeostasis, promoting the continuous adaptation of the T cell lymphoid space.