Correlation between mRNA expression of Th1/Th2 cytokines and their specific transcription factors in human helper T-cell clones.
The mechanisms that underlie Th1/Th2 differentiation of human T cells are incompletely defined. In the present study, a panel of human T-cell clones was used to elucidate the relationship between Th1/Th2-specific transcription factors and cytokine production in human helper T cells. The mRNA expression level of T-bet, a Th1-specific transcription factor, was higher in Th1 clones than in Th2 clones. In contrast, inducible expression of Th2-specific transcription factors (GATA-3 and c-Maf) in Th2 clones was higher than that in Th1 clones. The expression level of T-bet in various T-cell clones was positively correlated with that of IFN-gamma and negatively correlated with that of Th2 cytokines, particularly IL-4. Interestingly, the expression of IL-3 and IL-13, but not of other Th2 cytokines IL-4 and IL-5, was strongly correlated with GATA-3 mRNA levels. A reduction of GATA-3 using RNA interference technology suppressed, whereas overexpression of GATA-3 enhanced, the expression of IL-3 and IL-13. In conclusion, the level of T-bet expression is correlated with Th1/Th2 polarization status, whereas GATA-3 is a crucial factor in determining the IL-3 and IL-13 producing capacity of human T cells.
Kitamura
Noriko
N
Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan.
Kaminuma
Osamu
O
Mori
Akio
A
Hashimoto
Tomomi
T
Kitamura
Fujiko
F
Miyagishi
Makoto
M
Taira
Kazunari
K
Miyatake
Shoichiro
S
D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics; D007377:Interleukin-3 / Q000096:biosynthesis / Q000235:genetics; D019169:Jurkat Cells; D012333:RNA, Messenger / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000098815:T-bet Transcription Factor
D016207:Cytokines; D018793:Interleukin-13; D007377:Interleukin-3; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors