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Memory and flexibility of cytokine gene expression as separable properties of human TH1 and TH2 lymphocytes

Nature Immunologyvolume 4pages7886 (2003) | Download Citation

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Abstract

CD4+ T cell priming under T helper type I (TH1) or TH2 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 TH1 and TH2 cells acetylated and expressed the alternative gene when stimulated under opposite TH conditions. Such cytokine flexibility was absent in a subset of TH2 cells that failed to up-regulate T-bet and to express interferon-γ when stimulated under TH1 conditions. Thus, most human CD4+ T cells retain both memory and flexibility of cytokine gene expression.

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Acknowledgements

We thank D. Jarrossay for cell sorting; members of Natoli's lab and of Amaxa Biosystems GmbH for help with transfection experiments; and A. Gett and C. Mackay for critical reading and suggestions. Supported, in part, by the European Community (contract number QLK2-CT-201-01205); the San Salvatore Foundation (M.M.) and the Helmut Horten Foundation (A.L.).

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Affiliations

  1. Institute for Research in Biomedicine, Via Vincenzo Vela 6, Bellinzona, CH-6500, Switzerland

    • Mara Messi
    • , Isabella Giacchetto
    • , Antonio Lanzavecchia
    • , Gioacchino Natoli
    •  & Federica Sallusto
  2. R&D Center, BML, 1361-1 Matoba, Kawagoe, 350-1101, Saitama, Japan

    • Kinya Nagata

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Federica Sallusto.

Supplementary information

  1. Web Fig. 1.

    Increased histone acetylation and cytokine production upon secondary stimulation. TH1 and TH2 cell lines, which were stimulated once or twice in polarizing conditions, were analyzed for histone acetylation (a) and cytokine production upon PMA-iono stimulation (b). (PDF 129 kb)

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https://doi.org/10.1038/ni872

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