Recent research suggests that biopsies of human skin and bone marrow can provide the basis for the generation of a new, patient-specific T cell repertoire. T cells generated in skin cell cultures are diverse, mature, functional, and tolerant to self-MHC.
T cells play a central role in the human adaptive immune system, discriminating self from non-self, directing less specific elements of the immune system in the performance of effector functions, and serving as a repository for immunologic memory.
The ability to generate T cells suitable for use in human patients could lead to significant advances in the treatment of immunodeficiencies and malignancies. Such therapies have not yet been realized because the unique requirements for T cell development are difficult to replicate in vitro.
The authors, writing in the November issue of The Journal of Clinical Investigation 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.
The researchers from Harvard Skin Disease Research Center and Department of Dermatology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts, USA, found that 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 three transcription factors and a panel of autoantigens.
The authors conclude that 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.