Published online before print June 14, 2004

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(Journal of Leukocyte Biology. 2004;76:657-666.)
© 2004 by Society for Leukocyte Biology

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

Souyet Chang-Rodriguez^*, Rupert Ecker, Georg Stingl^* and Adelheid Elbe-Bürger^*,1

^* Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Austria; and
Competence Center for Bio Molecular Therapeutics, Vienna, Austria

¹ Correspondence: Department of Dermatology, DIAID, Medical University of Vienna, Brunner Str. 59, A-1235 Vienna, Austria. E-mail: adelheid.elbe-buerger{at}meduniwien.ac.at

To test whether reduced immune responsiveness in early life may be related to the immaturity of neonatal antigen-presenting cells, we comparatively assessed the phenotypic and functional characteristics of dendritic epidermal leukocytes (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 naive, allogeneic CD4⁺ and CD8⁺ T cells than LC. Freshly isolated DEL are twice as efficient as LC in the uptake of fluorescein isothiocyanate-conjugated 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 interleukin (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 differentiation of DEL into immunocompetent LC in intrauterine life and is at least partly responsible for the poor immune responsiveness of neonates.

Key Words: antigen presentation/processing • cytokines • cytokine receptors • dendritic cells • skin

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