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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AIRE Protein
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Autoantigens / biosynthesis
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Autoantigens / genetics
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Cell Differentiation / physiology*
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Cells, Cultured
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Clonal Deletion / physiology
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Forkhead Transcription Factors / biosynthesis
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Forkhead Transcription Factors / deficiency
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Forkhead Transcription Factors / genetics
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HLA Antigens / immunology
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Homeodomain Proteins / biosynthesis
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Homeodomain Proteins / genetics
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Humans
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Ligands
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Paired Box Transcription Factors / deficiency
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Paired Box Transcription Factors / genetics
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Notch / metabolism
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Self Tolerance / physiology
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Skin / cytology*
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Skin / immunology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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Thymus Gland / cytology
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Thymus Gland / immunology
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
Substances
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Autoantigens
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Forkhead Transcription Factors
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HLA Antigens
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HOXA3 protein, human
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Homeodomain Proteins
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Ligands
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Paired Box Transcription Factors
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Receptors, Antigen, T-Cell
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Receptors, Notch
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Transcription Factors
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Whn protein
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PAX1 transcription factor