Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice.
Thymocytes and thymic dendritic cell (DC) lineages develop simultaneously and may originate from a common intrathymic progenitor. Mice deficient for two growth factor receptor molecules [c-kit and the common cytokine receptor gamma chain (gamma(c))] lack all thymocytes including T cell progenitors. Despite this lack of pro-T cells, thymic DC compartments were identified in c-kit(-)gamma(c)(-) mice. Thus, c-kit- and gamma(c)-mediated signals are not essential to generate thymic DCs. In addition, pro-T cells do not appear to be obligatory progenitors of thymic DCs, because DC development is dissociated from the generation of thymocytes in these mice. Thymic DCs in c-kit(-)gamma(c)(-) mice are phenotypically and functionally normal. In contrast to wild-type mice, however, thymic DCs in c-kit(-)gamma(c)(-) and, notably, in RAG-2-deficient mice are CD8alpha(neg/low), indicating that CD8alpha expression on thymic DCs is not independent of thymocytes developing beyond the "RAG-block."
Rodewald
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Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland. hans-reimer.rodewald@medizin.uni-ulm.de
Brocker
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Haller
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D000818:Animals; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development / Q000276:immunology*
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D019009:Proto-Oncogene Proteins c-kit