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Murine Dendritic Cells Derived from Myeloid Progenitors of the Thymus Are Unable to Produce Bioactive IL-12p70¹

Laboratoire Immunochimie, Commissariat à l’Energie Atomique-Grenoble, Départment de Biologie Moléculaire et Structurale/Immunochimie, Institute National de la Santé et de la Recherche Médicale, Unité 238, Université Joseph Fourier, Grenoble, France

Dendritic cells (DC) are present at low density in the thymus where they mediate negative selection of self-reactive thymocytes. Previous reports suggest that thymic DC (TDC) are a single population of lymphoid-related DC. In this study, we documented the presence in the adult mouse thymus of an additional population of TDC exhibiting a myeloid phenotype (CD11c⁺ CD8^- CD11b⁺). This population, which can be purified, represented 20% of the total TDC and differs from the population of lymphoid TDC (CD11c⁺ CD8⁺ CD11b^-) by its incapacity to produce IL-12p70 under double stimulation by LPS and anti-CD40. Furthermore, using an original culture system allowing expansion of DC from myeloid progenitors, we demonstrated that DC exhibiting a similar myeloid phenotype can be derived from a common DC/macrophage progenitor resident in the adult mouse thymus. We found that, in contrast with myeloid splenic DC expanded in the same conditions, these cultured TDC were unable to produce IL-12p70 under double stimulation by LPS and anti-CD40 or LPS and IFN-. Thus, our results suggest that 1) adult mouse thymus contains at least two phenotypically and functionally distinct populations of DC; and 2) cultured myeloid DC derived from thymus and spleen differ by their ability to produce IL-12p70. The mechanisms underlying the differences in IL-12-secreting capacities of the cultured splenic and thymic DC are under current investigation.

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