In vivo tumor suppression activity by T cell-specific T-bet restoration.
T-box-containing protein expressed in T cells (T-bet) is a master transcription factor for the development of interferon (IFN) gamma-producing T helper 1 (Th1) cells and also functions in other immune cells including natural killer (NK), cytotoxic T lymphocytes and dendritic cells. T-bet-deficient mice increased susceptibility to viral infection and tumor development due to the defective functions of immune cells. T-bet is known to play a key role in NK-mediated antimetastatic response; however, it remains to be characterized whether T-bet is essential for in vivo tumor suppression mediated by T cells. Here, we have investigated in vivo tumor suppression effect of T-bet-restored T cells using T cell-specific and inducible T-bet transgenic mice generated in a T-bet-deficient background. T-bet-null mice increased susceptibility to tumor development, whereas induction of T cell-specific T-bet expression upon melanoma cell injection substantially suppressed tumor development by inducing IFNgamma production in T cells and tumor cell apoptosis. Late induction of T-bet expression in tumor-bearing mice produced comparable amounts of IFNgamma with control and significantly decreased tumor volume. In addition, increased melanoma lung metastasis in T-bet-deficient mice was strikingly inhibited by T-bet restoration in T cells. Intravenous injection of activated Th1 cells, not T-bet-null Th1 cells, attenuated metastatic melanoma progression, in addition, restoration of T-bet in T-bet-null Th1 cells certainly retrieved antimetastatic activity. These results suggest that T-bet expression in T cells is crucial for the control of tumor development and antimetastatic activity.
College of Pharmacy, Division of Life and Pharmaceutical Sciences and Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
Kihyun
K
Lee
Hyun Jung
HJ
Min
Eun Jung
EJ
Jang
Jeong-Ho
JH
Hong
Eun Sook
ES
Hwang
D000818:Animals; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D020825:T-Box Domain Proteins