Murine dendritic cells derived from myeloid progenitors of the thymus are unable to produce bioactive IL-12p70.
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(+) CD8alpha(-) CD11b(+)). This population, which can be purified, represented approximately 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-gamma. 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.
Martinon-Ego
C
C
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.
Berthier
R
R
Cretin
F
F
Collin
V
V
Laharie
A M
AM
Marche
P N
PN
D000818:Animals; D015415:Biomarkers; D002452:Cell Count; D002453:Cell Cycle / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D015415:Biomarkers; D018664:Interleukin-12