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

Human skin cells support thymus-independent T cell development

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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Newly generated T cells are tolerant to challenge with autologous, but n...
Newly generated T cells are tolerant to challenge with autologous, but not allogeneic, DCs. T cells produced in skin cell cultures from HPCs of bone marrow donor A were exposed to donor A–derived DCs during the process of T cell development. Donor A–derived lymphocytes were therefore examined for their ability to respond to DCs derived from the same donor (donor A) and a second, unrelated donor (donor B) in the MLR. Responses of PBMCs to the DCs of both donors are included to demonstrate the immunogenicity of both DC populations. Proliferation was assayed by BrdU incorporation on day 6 of the MLR. BrdU incorporation was detected via flow cytometry with gating on CD3+ T cells. PBMCs were derived from a third, unrelated donor. Error bars represent the SD of 3 measurements. A duplicate set of experiments produced similar results.