Immune suppressive activity and lack of T helper differentiation are differentially regulated in natural regulatory T cells.
The mechanism for controlling Th cytokine expression in natural regulatory T (nTreg) cells is unclear. Here, it was found that under polarizing conditions Foxp3 did not affect Th1 cell, partially inhibited Th17 cell, but greatly inhibited Th2 cell differentiation of conventional CD4 T cells. Under the polarizing conditions, nTreg cells failed to differentiate into Th2 and Th17 cells, but differentiated into IFN-gamma-producing cells. Such Foxp3-transduced CD4 T cells and nTreg cells expressed T-bet, GATA-3, or retinoic acid-related orphan receptor (ROR)gammat, and retroviral GATA-3 and RORgammat could not induce Th2 and Th17 differentiation from nTreg cells. However, regardless of their cytokine profiles, the Foxp3-transduced CD4 T cells and nTreg cells remained immune suppressive. These results suggested that it is possible to convert pathogenic Th cells to Treg-like cells for therapeutic application. In conclusion, our studies show that Foxp3 is sufficient for immune suppression, whereas the inhibition of cytokine expression requires additional mechanisms.
Zeng
Wei-ping
WP
Department of Biochemistry and Microbiology, Joan C Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA. zongb1@excite.com
Chang
Chawnshang
C
Lai
Jiann-jyh
JJ
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors; D051858:Forkhead Transcription Factors / Q000502:physiology*; D007109:Immunity; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D007371:Interferon-gamma