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Published online before print May 15, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0207111

Received for publication February 13, 2007.
Revised March 30, 2007.
Accepted for publication April 27, 2007.

Article

Induction of a distinct CD8 Tnc17 subset by transforming growth factor- and interleukin-6

Shih-Jen Liu ^*, Jy-Ping Tsai ^*, Chia-Rui Shen , Yuh-Pyng Sher , Chia-Ling Hsieh , Yu-Ching Yeh ^*, Ai-Hsiang Chou ^*, Shu-Rung Chang ^*, Kuang-Nan Hsiao ^*, Feng-Wei Yu , and Hsin-Wei Chen ^*@

*Vaccine Research and Development Center, National Health Research Institutes, Miaoli, Taiwan, Republic of China; Graduate Institute of Medical Biotechnology, Chang Gung University, Tao-Yuan, Taiwan, Republic of China; Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China; and Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China

^@ To whom correspondence should be addressed. E-mail: chenhw{at}nhri.org.tw.

	Abstract

Cross-talk between TGF- and IL-6 has been shown to direct the differentiation of CD4⁺ cells into special IL-17-secreting cells, which are termed Th17 cells. In this study, we demonstrated that TGF- and IL-6 could stimulate CD8⁺ cells to differentiate into noncytotoxic, IL-17-producing cells in MLC. These IL-17-producing CD8⁺ cells exhibit a unique granzyme B^-IFN-^-IL-10^- phenotype. The mRNA level of Th2/Tc2 transcription factors GATA3 and Th1/Tc1 transcription factors T-bet as well as its target Hlx is decreased in CD8⁺ cells from TGF-- and IL-6-treated MLC. In addition, these CD8⁺ cells display a marked up-regulation of retinoic acid-related orphan receptor-t, a key IL-17 transcription factor. These results demonstrate that the existence of an IL-17-producing CD8⁺ subset belongs to neither the Tc1 nor the Tc2 subset and can be categorized as a Tnc17 subset.

Key Words: IL-17 • mixed lymphocyte culture • cytotoxic T lymphocyte

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