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Human skin cells support thymus-independent T cell development
Rachael A. Clark, … , Rebecca Dowgiert, Thomas S. Kupper
Rachael A. Clark, … , Rebecca Dowgiert, Thomas S. Kupper
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3239-3249. https://doi.org/10.1172/JCI24731.
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Research Article Immunology Article has an altmetric score of 3

Human skin cells support thymus-independent T cell development

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Abstract

Thymic tissue has previously been considered a requirement for the generation of a functional and diverse population of human T cells. We report that fibroblasts and keratinocytes from human skin arrayed on a synthetic 3-dimensional matrix support the development of functional human T cells from hematopoietic precursor cells in the absence of thymic tissue. Newly generated T cells contained T cell receptor excision circles, possessed a diverse T cell repertoire, and were functionally mature and tolerant to self MHC, indicating successful completion of positive and negative selection. Skin cell cultures expressed the AIRE, Foxn1, and Hoxa3 transcription factors and a panel of autoantigens. Skin and bone marrow biopsies can thus be used to generate de novo functional and diverse T cell populations for potential therapeutic use in immunosuppressed patients.

Authors

Rachael A. Clark, Kei-ichi Yamanaka, Mei Bai, Rebecca Dowgiert, Thomas S. Kupper

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Figure 5

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Expression of delta-like Notch ligands in human keratinocytes. (A) Secti...
Expression of delta-like Notch ligands in human keratinocytes. (A) Sections of normal human skin stained for delta-like Notch ligands demonstrated abundant staining of suprabasal epidermal keratinocytes but no staining of dermal fibroblasts. Magnification: ×10. (B) Keratinocytes freshly isolated from skin expressed delta-like ligands, but fibroblasts lacked expression. SSC-H, side scatter. (C) Cultured keratinocytes contained a mixture of large differentiating cells that expressed high levels of delta-like Notch ligands (green) and smaller, basaloid cells that were negative for delta-like ligand expression. Magnification: ×4. (D) Keratinocytes cultured under high-density conditions that encouraged differentiation expressed delta-like ligands.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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