Autocrine IL-10 partially prevents differentiation of neonatal dendritic epidermal leukocytes into Langerhans cells.
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.
Chang-Rodriguez
Souyet
S
Department of Dermatology, DIAID, Medical University of Vienna, Brunner Str. 59, A-1235 Vienna, Austria.
Ecker
Rupert
R
Stingl
Georg
G
Elbe-Bürger
Adelheid
A
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D019898:Autocrine Communication / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D048429:Cell Size / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000254:growth & development / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D016753:Interleukin-10