The Journal of Experimental Medicine
StemCell Technologies
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Published online May 12, 2008
doi:10.1084/jem.20072057
The Journal of Experimental Medicine
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Suto et al.
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ARTICLE

 Development and characterization of IL-21–producing CD4+ T cells

Akira Suto1,2, Daisuke Kashiwakuma2, Shin-ichiro Kagami1,2, Koichi Hirose2, Norihiko Watanabe2, Kotaro Yokote3, Yasushi Saito3, Toshinori Nakayama4, Michael J. Grusby5, Itsuo Iwamoto6, and Hiroshi Nakajima1,2

1 Department of Molecular Genetics, Graduate School of Medicine, 2 Department of Allergy and Clinical Immunology, Chiba University Hospital, 3 Department of Clinical Cell Biology, and 4 Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670 Japan
5 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
6 Research Center for Allergy and Clinical Immunology, Asahi General Hospital, Asahi, Chiba, 289-2511 Japan

CORRESPONDENCE Hiroshi Nakajima: nakajimh{at}faculty.chiba-u.jp

It has recently been shown that interleukin (IL)-21 is produced by Th17 cells, functions as an autocrine growth factor for Th17 cells, and plays critical roles in autoimmune diseases. In this study, we investigated the differentiation and characteristics of IL-21–producing CD4+ T cells by intracellular staining. Unexpectedly, we found that under Th17-polarizing conditions, the majority of IL-21–producing CD4+ T cells did not produce IL-17A and -17F. We also found that IL-6 and -21 potently induced the development of IL-21–producing CD4+ T cells without the induction of IL-4, IFN-{gamma}, IL-17A, or IL-17F production. On the other hand, TGF-β inhibited IL-6– and IL-21–induced development of IL-21–producing CD4+ T cells. IL-2 enhanced the development of IL-21–producing CD4+ T cells under Th17-polarizing conditions. Finally, IL-21–producing CD4+ T cells exhibited a stable phenotype of IL-21 production in the presence of IL-6, but retained the potential to produce IL-4 under Th2-polarizing conditions and IL-17A under Th17-polarizing conditions. These results suggest that IL-21–producing CD4+ T cells exhibit distinct characteristics from Th17 cells and develop preferentially in an IL-6–rich environment devoid of TGF-β, and that IL-21 functions as an autocrine growth factor for IL-21–producing CD4+ T cells.

A. Suto and D. Kashiwakuma contributed equally to this work.


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