The c-kit+ maturation pathway in mouse thymic T cell development: lineages and selection.
Positive selection of T cells begins with TCR alpha beta lo thymic progenitors. Here, we show that the most efficient TCRlo progenitors are c-kit+ with intermediate levels of CD4 and CD8 (DPint). Positive selection of DPint TCRlo c-kit+ cells results in TCRmed CD69+ c-kit+ transitional intermediates that show increased TCRV beta frequencies to selecting superantigen (SAg) that are committed to the CD4 or CD8 pathway. The cells on the c-kit+ maturation pathway maintain Bcl-2 expression. Most DPint c-kit+ progenitors fail positive selection, and become DPhi c-kit- cells that lose Bcl-2 expression. Some DPhi c-kit blast cells can be salvaged to produce mature single-positive (SP) cells. DPint c-kit+ maturation to SP cells can occur in <12 hr in vitro on thymic stromal monolayers.
Akashi
K
K
Department of Pathology, Stanford University School of Medicine, California 94305, USA.
Weissman
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IL
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D016130:Immunophenotyping; D007267:Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D017252:CD3 Complex; D019253:Proto-Oncogene Proteins c-bcl-2; D019009:Proto-Oncogene Proteins c-kit