CONSTITUTIVE AND INDUCIBLE EXPRESSION OF INTERLEUKIN-6 BY LANGERHANS CELLS AND LYMPH-NODE DENDRITIC CELLS

During the induction phase of contact sensitization and other cutaneou s immune responses a proportion of epidermal Langerhans cells (LC) is induced to leave the skin and migrate via afferent lymphatics to lymph nodes draining the site of exposure. The cells that accumulate in dra ining nodes have acquired the characteristics of immunostimulatory den dritic cells and effectively present antigen to responsive T lymphocyt es. In the present study we have questioned whether LC in the epidermi s and the lymph node dendritic cells into which they develop express i nterleukin-6 (IL-6), a cytokine that has been shown to serve as an imp ortant costimulator of T lymphocyte activation. In situ immunocytochem ical analyses using a biotin-streptavidin staining technique revealed that dendritic cells resident in the epidermis of untreated mice const itutively express this cytokine. Keratinocytes expressed detectable IL -6 only following local exposure to the contact allergen oxazolone. Su ch treatment also appeared to enhance the expression by epidermal dend ritic cells of this cytokine. Analyses of unfractionated and LC-enrich ed and -depleted populations of epidermal cells revealed a close corre lation between major histocompatibility complex (MHC) class II (Ia) an tigen expression and staining for IL-6, implicating LC as the sole or major source of this cytokine in unstimulated epidermis. Finally, comp ared with tissue isolated from mice treated with vehicle alone, draini ng lymph nodes prepared from animals 18 hr following sensitization wit h oxazolone displayed a substantial increase in both the frequency of dendritic cells and the number of IL-6(+) cells within the paracortex. These data demonstrate that resident epidermal LC and the dendritic c ells into which they develop are important sources of IL-6. Their cons titutive and inducible expression of this cytokine will facilitate the induction of cutaneous immune responses.