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DNA methylation secures CD4+ and CD8+ T cell lineage borders

Nature Immunology volume 16, pages 681–683 (2015)Cite this article

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Dynamic control of DNA methylation in the Cd4 locus serves an important role in reinforcing the binary fate stability of helper and cytotoxic T cells.

Over the past three decades, studies of a variety of experimental organisms have resulted in a tremendous advancement in understanding of the molecular mechanisms of differentiation and commitment of various cell lineages. However, little is known about the mechanistic basis of the maintenance of differentiated cellular states1. Helper CD4+ T cells and cytotoxic CD8+ T cells are two principal lineages of T lymphocytes with distinct roles in the adaptive immune response. Signaling via the T cell antigen receptor induced by self peptides presented by major histocompatibility complex class II or class I molecules on thymic cortical epithelial cells prompts common thymic progenitor cells to initiate and establish corresponding functional programs specific to the helper lineage or cytotoxic lineage, including expression of the co-receptors CD4 or CD8, respectively2. In this issue of Nature Immunology, a study by Sellars et al. reveals that dynamic regulation of DNA methylation at a distinct regulatory element in the Cd4 locus serves a critical role in reinforcing differential expression of CD4 and, therefore, helper and cytotoxic T cell fate 'choice'3. These observations highlight a key role for DNA methylation in maintaining differentiated cellular states.

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Figure 1: Epigenetic control of the stability of helper CD4+ and cytotoxic CD8+ T cell lineages.

Marina Corral Spence/Nature Publishing Group

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Authors and Affiliations

  1. Yongqiang Feng and Alexander Y. Rudensky are with the Howard Hughes Medical Institute and Immunology Program, Ludwig Center at Memorial Sloan-Kettering Cancer Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.,

    Yongqiang Feng & Alexander Y Rudensky

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  1. Yongqiang Feng
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  2. Alexander Y Rudensky
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Correspondence to Alexander Y Rudensky.

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Feng, Y., Rudensky, A. DNA methylation secures CD4+ and CD8+ T cell lineage borders. Nat Immunol 16, 681–683 (2015). https://doi.org/10.1038/ni.3207

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