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Self-reactivity in thymic double-positive cells commits cells to a CD8αα lineage with characteristics of innate immune cells

Nature Immunology volume 5, pages 597–605 (2004)Cite this article

Abstract

Thymocytes displaying self-reactive T cell receptors usually undergo negative selection in the thymus. Here we demonstrate that agonist peptides can promote positive selection of immature double-positive thymocytes into distinct lineages, varying with the agonist concentration and the animal's age. Microarray gene expression analyses showed broad transcriptional alterations in a set of transcripts associated with the innate immune system, as well as silencing of CD8β expression. The resulting CD8αα T cells showed a rapid effector cytokine response. Hence, T cells displaying self-reactive receptors can have the gene expression profile and phenotypic characteristics of innate immune cells.

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Figure 1: Agonist peptide restores positive selection in defective thymi from HY TCR–transgenic female mice.
Figure 2: The phenotype of mature cells elicited by agonist peptide varies with dose in RTOC and age in vivo.
Figure 3: Mature CD8αα cells of other TCR specificities are elicited by their cognate peptide.
Figure 4: CD8αα cells have a distinct gene expression profile.
Figure 5: Integrated set of genes involved in innate or NK function induced by agonist in TCRαβ T cells.
Figure 6: Innate-like character of the transcriptional patterns in CD8αα cells.
Figure 7: The density of TCR triggering in developing thymocytes engages an innate or an adaptive differentiation program.

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Acknowledgements

We thank L. Poirot, E. Venanzi and A. Goldrath for microarray data sets; Q.-M. Pham and V. Bruklich for help with the mice; G. Losyev for flow cytometry; R. Park for help with the data analysis; and the T cell group for discussions. Supported by the National Institutes of Health (1R01AI51530), by core services from the National Institute of Diabetes and Digestive and Kidney Diseases–funded Diabetes Endocrinology Research Center (Joslin Diabetes Center) and by the Japan Society for the Promotion of Science and the Uehara Memorial Foundation (T.Y.).

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Authors and Affiliations

  1. Section on Immunology and Immunogenetics, Joslin Diabetes Center,

    Tetsuya Yamagata, Diane Mathis & Christophe Benoist

  2. Department of Medicine, Brigham and Women's Hospital,

    Tetsuya Yamagata, Diane Mathis & Christophe Benoist

  3. Harvard Medical School, One Joslin Place, Boston, 02215, Massachusetts, USA

    Tetsuya Yamagata, Diane Mathis & Christophe Benoist

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Correspondence to Diane Mathis or Christophe Benoist.

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Yamagata, T., Mathis, D. & Benoist, C. Self-reactivity in thymic double-positive cells commits cells to a CD8αα lineage with characteristics of innate immune cells. Nat Immunol 5, 597–605 (2004). https://doi.org/10.1038/ni1070

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