Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function

Cytokines are important in the regulation of haematopoiesis and immune resp onses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expres sed in BaF3 cells, which created a functional assay for ligand detection an d cloning. Conditioned media from activated human CD3(+) T cells supported proliferation of the assay cell line. We constructed a complementary DNA ex pression library from activated human CD3+ T cells, and identified a cytoki ne with a four-helix-bundle structure using functional cloning. This cytoki ne is most closely related to IL2 and IL15, and has been designated IL21 wi th the receptor designated IL21R. In vitro assays suggest that IL21 has a r ole in the proliferation and maturation of natural killer (NK) cell populat ions from bone marrow, in the proliferation of mature B-cell populations co -stimulated with anti-CD40, and in the proliferation of T cells co-stimulat ed with anti-CD3.