Thymic stroma is required for the development of human T cell lineages in vitro.
Development of the T cell lineage is characterized by the homing of hematopoietic precursors to thymus, followed by their acquisition of receptors for antigen. T cell receptors are alpha beta or gamma delta heterodimers associated with CD3 (TCR-CD3). Very early T cell precursors in humans have been characterized as CD7+ 45+ cells which lack the T cell differentiation antigens CD1, CD2, CD3, CD4, and CD8. A phenotypically equivalent early thymocyte population also occurs in postnatal life, and we have previously shown that interleukin 2 (IL2) promotes the development in vitro of both the alpha beta and the gamma delta T cells from these early thymocytes. Here we have analyzed the requirements of the induction of the IL2 pathway in early thymocytes, and their developmental potential. We show that: (i) thymic stromal cells, which are present in thymocyte suspensions, are necessary to induce the IL2 pathway and the development of alpha beta or gamma delta T cell lineages from early thymocytes in vitro; and (ii) when removed from the in vivo environment, early thymocytes can develop in vitro into TCR-CD3- cells of the natural killer (NK) lineage. We conclude that CD7+ 45+, CD1-2-3-4-8- early thymocytes are multipotential progenitors that, at least, have the capacity to develop into alpha beta or gamma delta T cell and NK lineages. The analysis of the mechanisms of generation and selection of human T and NK cell diversity, not feasible in bone marrow cultures, is now possible.
de la Hera
A
A
Basel Institute for Immunology, Switzerland.
Marston
W
W
Aranda
C
C
Toribio
M L
ML
Martinez
C
C
D000945:Antigens, Differentiation, T-Lymphocyte; D002454:Cell Differentiation; D002455:Cell Division; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000166:cytology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell