Memory and flexibility of cytokine gene expression as separable properties of human T(H)1 and T(H)2 lymphocytes.
CD4+ T cell priming under T helper type I (T(H)1) or T(H)2 conditions gives rise to polarized cytokine gene expression. We found that in these conditions human naive T cells acquired stable histone hyperacetylation at either the Ifng or Il4 promoter. Effector memory T cells showed polarized cytokine gene acetylation patterns in vivo, whereas central memory T cells had hypoacetylated cytokine genes but acquired polarized acetylation and expression after appropriate stimulation. However, hypoacetylation of the nonexpressed cytokine gene did not lead to irreversible silencing because most T(H)1 and T(H)2 cells acetylated and expressed the alternative gene when stimulated under opposite T(H) conditions. Such cytokine flexibility was absent in a subset of T(H)2 cells that failed to up-regulate T-bet and to express interferon-gamma when stimulated under T(H)1 conditions. Thus, most human CD4+ T cells retain both memory and flexibility of cytokine gene expression.
Messi
Mara
M
Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
Giacchetto
Isabella
I
Nagata
Kinya
K
Lanzavecchia
Antonio
A
Natoli
Gioacchino
G
Sallusto
Federica
F
D000107:Acetylation; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D050990:GATA3 Transcription Factor; D015870:Gene Expression; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D011401:Promoter Regions, Genetic; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000098815:T-bet Transcription Factor
D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D006657:Histones; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA