Thymic stroma is required for the development of human T cell lineages in vitro |
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Authors: | de la Hera Antonio; Marston Wendy; Aranda Crisanto; Toribio Marie-Luisa; Martinez-A Carlos |
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Institution: | Basel Institute for Immunology Grenzacherstrasse 487, Basel 4005, Switzerland
1 Coulter Cientifica, Mostoles, Madrid, Spain
2 Instituto de Biologia Molecular, CSIC, Universidad Autonoma de Madrid Cantoblanco, Madrid 28049, Spain |
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Abstract: | Development of the T cell lineage is characterized by the homingof hematopoietic precursors to thymus, followed by their acquisitionof receptors for antigen. T cell receptors are ß or heterodimers associated with CD3 (TCR-CD3). Very early T cellprecursors in humans have been characterized as CD7+45+ cellswhich lack the T cell differentiation antigens CD1, CD2, CD3,CD4, and CD8. A phenotypically equivalent early thymocyte populationalso occurs in postnatal life, and we have previously shownthat interleukin 2 (IL2) promotes the development in vitro ofboth the ß and the T cells from these early thymocytes.Here we have analyzed the requirements of the induction of theIL2 pathway in early thymocytes, and their developmental potential.We show that: (I) thymic stromal cells, which are present inthymocyte suspensions, are necessary to induce the IL2 pathwayand the development of ß or T cell lineages fromearly thymocytes in vitro; and (II) when removed from the invivo environment, early thymocytes can develop in vitro intoTCR-CD3– cells of the natural killer (NK) lineage. Weconclude that CD7+45+, CD1–2–3–4–8–early thymocytes are multipotential progenitors that, at least,have the capacity to develop into ß or T cell andNK lineages. The analysis of the mechanisms of generation andselection of human T and NK cell diversity, not feasible inbone marrow cultures, is now possible. |
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Keywords: | ß" target="_blank">gif" ALT="{alpha}" BORDER="0">ß and 76 gif" ALT="{gamma}" BORDER="0"> cells" target="_blank">gif" ALT="{delta}" BORDER="0"> cells natural killer cells interleukins 1 2 3 and 4 hematopoietic progenitors differentiation pathways |
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