Autocrine IL-10 partially prevents differentiation of neonatal dendritic epidermal leukocytes into Langerhans cells

To test whether reduced immune re- sponsiveness in early life may be related to the immaturity of neonatal antigen-presenting cells, we comparatively assessed the phenotypic and func- tional characteristics of dendritic epidermal leuko- cytes (DEL) and epidermal Langerhans cells (LC) in newborn (NB) and adult mice, respectively. We report that purified, 3-day-cultured DEL do not acquire the morphology and phenotype typical of LC and are significantly weaker stimulators of na- ive, allogeneic CD4 and CD8 T cells than LC. Freshly isolated DEL are twice as efficient as LC in the uptake of fluorescein isothiocyanate-conju- gated tracers but are not able to present these to antigen-specific T cell hybridomas. To clarify the underlying cause, cytokine expression of NB and adult epidermal cells (EC) was examined. We found that DEL express considerable amounts of inter- leukin (IL)-10, that IL-10 in NB EC supernatants partially inhibits LC maturation, and that DEL- enriched EC from IL-10 / mice induce stronger primary T cell responses compared with those from IL-10 / mice. We conclude that IL-10 is one of the factors preventing maturation and dif- ferentiation of DEL into immunocompetent LC in intrauterine life and is at least partly responsible for the poor immune responsiveness of neonates. J. Leukoc. Biol. 76: 657- 666; 2004.