Interleukin 21: A Key Player in Lymphocyte Maturation

The common γ chain family of cytokine receptors plays a plethora of roles during the early development, activation, and terminal differentiation of the lymphocyte lineages. The most recently identified member of this family, the IL-21R, is expressed to varying degrees on B, T lymphocytes, and natural killer (NK) cells, whereas IL-21, is reportedly only produced by activated CD4+ T cells. In keeping with this expression pattern the IL-21:IL-21R interaction is important for the latter stages and function of all three lymphoid lineages. IL-21 is a regulator of B-cell differentiation to plasma cells as well as immunoglobulin class switching. In contrast, within the T-cell lineage, IL-21 acts as a co-stimulator of proliferation, enhances memory response, and modulates homeostasis. Within the innate immune system IL-21 has a role in the terminal differentiation of NK cells, enhancing cytotoxic function while also decreasing cellular viability. These immune maturation and stimulating functions have resulted in IL-21 being tested in a variety of models of immunity. In these contexts, IL-21 has shown very promising efficacy in a number of antitumor immune responses mediated by NK and or T lymphocytes.