Induction of a distinct CD8 Tnc17 subset by transforming growth factor-beta and interleukin-6.
Cross-talk between TGF-beta 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-beta 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-gamma(-)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-beta- and IL-6-treated MLC. In addition, these CD8(+) cells display a marked up-regulation of retinoic acid-related orphan receptor-gammat, 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.
Liu
Shih-Jen
SJ
Vaccine Research and Development Center, National Health Research Institutes, Miaoli, Taiwan, China.
Tsai
Jy-Ping
JP
Shen
Chia-Rui
CR
Sher
Yuh-Pyng
YP
Hsieh
Chia-Ling
CL
Yeh
Yu-Ching
YC
Chou
Ai-Hsiang
AH
Chang
Shu-Rung
SR
Hsiao
Kuang-Nan
KN
Yu
Feng-Wei
FW
Chen
Hsin-Wei
HW
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016827:CD8 Antigens; D020381:Interleukin-17; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta