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 γ chain (γ(c))] lack all thymocytes including T cell progenitors. Despite this lack of pro-T cells, thymic DC compartments were identified in c-kit(−)γ(c)(−) mice. Thus, c-kit- and γ(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(−)γ(c)(−) mice are phenotypically and functionally normal. In contrast to wild-type mice, however, thymic DCs in c-kit(−)γ(c)(−) and, notably, in RAG-2-deficient mice are CD8α(neg/low), indicating that CD8α expression on thymic DCs is not independent of thymocytes developing beyond the “RAG-block.”