Modulation of the population density of identifiable epidermal Langerhans cells associated with enhancement or suppression of cutaneous immune reactivity.

Abstract

The epidermis on the backs or ears of DBA/2 mice treated for 7 days with a 20% concentration of monobenzyl ether of hydroquinone (MBEH) had a significantly greater population density of ATPase- and Ia-positive cells compared with control mice treated with diluent. There was no decrease or increase in ATPase- or Ia-positive cells at sites distal from the treated tissue. This increase in population density of Langerhans cells was associated with a significant increase in functional afferent immune reactivity measured by allergic contact hypersensitivity. We also found evidence for enhanced efferent immune reactivity. Animals treated on the ears for 7 days with MBEH were sensitized to DNFB on untreated back. MBEH treated ears with more Ia-positive Langerhans cells demonstrated a threefold greater increase in swelling after the DNFB challenge than the control mice. Results of other studies suggest that the afferent and efferent enhanced immune reactivity produced by MBEH are local effects. We postulated that MBEH produced its effects by activating the oxidation of arachidonic acid (AA) to prostaglandins. To test this, we applied AA to mouse skin. AA has a biphasic effect on epidermal Langerhans cells: in low doses it increases their number; in high amounts it decreases the number of identifiable cells with either the Ia or the ATPase technique. An increased population density of identifiable epidermal Langerhans cells induced with AA was correlated with an increase in afferent and efferent immune reactivity. In contrast, reduction of Langerhans cells with larger amounts of AA suppress the afferent and efferent limb of the immune response. DNFB applied to skin with decreased Langerhans cell density from AA induced a state that mimics immune tolerance. The findings are significant because we report the only method to either increase or decrease the population density of Langerhans cells: and to modulate up or down the afferent or efferent limbs of the cutaneous immune response. Our results also suggest that the Langerhans cell may be involved in the efferent limb of the immune efferent response. These effects may be modulated in part by products of AA metabolism.