T-Bet expression and failure of GATA-3 cross-regulation lead to default production of IFN-gamma by gammadelta T cells.
gammadelta T cells predominantly produce IFN-gamma upon activation. To determine the basis for default production of IFN-gamma by gammadelta T cells, we analyzed the transcription factors T-box expressed in T cells (T-bet) and GATA-3. T-bet, absent in naive cells, was induced upon TCR signaling, with IFN-gamma production. T-bet also regulated IL-4 synthesis, as gammadelta cells isolated from T-bet-deficient mice displayed enhanced IL-4 levels with reduced IFN-gamma production. Notably, T-bet expression after TCR signaling in gammadelta cells was not down-regulated by IL-4, in conjunction with a higher ratio of T-bet:GATA-3 expression than that found in CD4(+) T cells. Indeed, overexpression of GATA-3 failed to inhibit IFN-gamma secretion in gammadelta cells to the degree seen in CD4(+) T cells. These results indicate that T-bet enhances IFN-gamma secretion and suppresses IL-4 secretion in gammadelta cells, and that GATA-3 fails to counterbalance T-bet-mediated IFN-gamma production, accounting for the default synthesis of IFN-gamma by these T lymphocytes.
Yin
Zhinan
Z
Sections of. Rheumatology and Pulmonary and Critical Care Medicine, Department of Medicine, and Section of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Chen
ChangHung
C
Szabo
Susanne J
SJ
Glimcher
Laurie H
LH
Ray
Anuradha
A
Craft
Joe
J
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D020825:T-Box Domain Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D000098815:T-bet Transcription Factor
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma