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Interleukin 15 controls the generation of the restricted T cell receptor repertoire of γδ intestinal intraepithelial lymphocytes

Nature Immunology volume 6, pages 1263–1271 (2005)Cite this article

Abstract

The γδ T cells are prevalent in the mucosal epithelia and are postulated to act as 'sentries' for maintaining tissue integrity. What these γδ T cells recognize is poorly defined, but given the restricted T cell receptor (TCR) repertoire, the idea that they are selected by self antigens of low complexity has been widely disseminated. Here we present data showing that the generation of the restricted TCR variable γ-region gene repertoire of intestinal intraepithelial lymphocytes was regulated by interleukin 15, which induced local chromatin modifications specific for the variable γ-region gene segment and enhanced accessibility conducive to subsequent targeted gene rearrangement. This cytokine-directed tissue-specific TCR repertoire formation probably reflects distinct TCR repertoire selection criteria for γδ and αβ T cell lineages adopted for different antigen-recognition strategies.

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Figure 1: The generation of Vγ5+ γδ thymocytes is controlled by IL-15.
Figure 2: Histone acetylation patterns correlate with Vγ gene usage.
Figure 3: IL-15 regulates transcriptional activity and alters histone chromatin modification specifically at the Vγ5 gene segment independent of RAG-mediated Tcrg rearrangement in thymocytes.
Figure 4: Comparison of Vγ5 gene segment–specific transcriptional activity and chromatin accessibility in the intestine versus the thymus.
Figure 5: Increased AcH3 modification at the Vγ5 gene segment that results from Il15 transgene expression is dependent on FL-STAT5.

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Acknowledgements

We thank D.H. Raulet for initial support of this work; C. Chambers for discussions; M. Caligiuri, J. Ihle and J. Peschon for Il15-transgenic, FL-STAT5–deficient and Il15−/− mice, respectively; D.H. Raulet, W. Held, L. Berg, M. Bix and members of the lab for critical comments on the manuscript; and K. Pinault and T. Mascenik for assistance with animal husbandry.

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  1. Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, 01655, Massachusetts, USA

    Hang Zhao, Hai Nguyen & Joonsoo Kang

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Correspondence to Joonsoo Kang.

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Supplementary information

Supplementary Fig. 1

Effects of IL-15 in the generation of Vγ5+ γδ T cells. (PDF 265 kb)

Supplementary Table 1

DNA sequences of PCR primers. (PDF 68 kb)

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Zhao, H., Nguyen, H. & Kang, J. Interleukin 15 controls the generation of the restricted T cell receptor repertoire of γδ intestinal intraepithelial lymphocytes. Nat Immunol 6, 1263–1271 (2005). https://doi.org/10.1038/ni1267

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