Human skin cells support thymus-independent T cell development.
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.
Clark
Rachael A
RA
Harvard Skin Disease Research Center and Department of Dermatology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
Yamanaka
Kei-ichi
K
Bai
Mei
M
Dowgiert
Rebecca
R
Kupper
Thomas S
TS
D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D006680:HLA Antigens / Q000276:immunology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008024:Ligands; D051761:Paired Box Transcription Factors / Q000172:deficiency / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D017634:Self Tolerance / Q000502:physiology; D012867:Skin / Q000166:cytology* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000096927:AIRE Protein
D001324:Autoantigens; D051858:Forkhead Transcription Factors; D006680:HLA Antigens; D018398:Homeodomain Proteins; D008024:Ligands; D051761:Paired Box Transcription Factors; D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch; D014157:Transcription Factors; D000096927:AIRE Protein; C489832:HOXA3 protein, human; C090140:Whn protein; C070835:PAX1 transcription factor