Article
Nature 408, 57-63 (2 November 2000) | doi:10.1038/35040504; Received 19 July 2000; Accepted 13 September 2000
Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function
Julia Parrish-Novak1, Stacey R. Dillon2, Andrew Nelson2, Angie Hammond1, Cindy Sprecher1, Jane A. Gross2, Janet Johnston2, Karen Madden1, Wenfeng Xu1, Jim West3, Sara Schrader1, Steve Burkhead1, Mark Heipel1, Cameron Brandt1, Joseph L. Kuijper1, Janet Kramer1, Darrell Conklin4, Scott R. Presnell4, Jon Berry3, Faith Shiota2, Susan Bort2, Kevin Hambly2, Sherri Mudri2, Chris Clegg2, Margaret Moore5, Francis J. Grant4, Catherine Lofton-Day5, Teresa Gilbert5, Fenella Raymond5, Andrew Ching4, Lena Yao5, Deb Smith5, Philippa Webster5, Theodore Whitmore5, Mark Maurer5, Kenneth Kaushansky6, Rick D. Holly1 & Don Foster1
- Departments of
- Functional Cloning,
- Immunology,
- Protein Biochemistry,
- Biomolecular Informatics, and
- Genetics, ZymoGenetics, Inc., 1201 Eastlake Avenue E., Seattle, Washington 98102, USA
- Division of Hematology, Box 35 7710, University of Washington, School of Medicine, 1959 NE Pacific Street, Seattle, Washington 98195, USA
Correspondence to: Don Foster1 Correspondence and requests for materials should be addressed to D.F. (e-mail: Email: fosterd@zgi.com). Sequences described have been submitted to GenBank under accession nos AF254067, AF254068, AF254069 and AF254070.
Abstract
Cytokines are important in the regulation of haematopoiesis and immune responses, 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 expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.
