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Published online before print May 15, 2007

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(Journal of Leukocyte Biology. 2007;82:354-360.)
© 2007 by Society for Leukocyte Biology

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

Shih-Jen Liu^*,1, Jy-Ping Tsai^*,1, 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^*,2

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

² Correspondence: Vaccine Research and Development Center, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, China. E-mail: chenhw{at}nhri.org.tw

Cross-talk between TGF-β 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-β 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/T cytotoxic 2 (Tc2) transcription factors GATA3 and Th1/Tc1 transcription factors T-box expressed in T cell (T-bet) as well as its target H2·O-like homeobox (Hlx) is decreased in CD8⁺ cells from TGF-β- 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 T noncytotoxic 17 (Tnc17) subset.

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

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