INDUCTION OF LOW ZONE TOLERANCE TO CONTACT ALLERGENS IN MICE DOES NOTREQUIRE FUNCTIONAL LANGERHANS CELLS

Epidermal Langerhans cells are known to be the major controlling eleme nt in the development of contact hypersensitivity. Haptenic molecules permeating the skin are taken up locally by Langerhans cells and then presented to T lymphocytes in the regional lymph nodes. Despite the pr esence of functional Langerhans cells, however, subsensitizing doses o f hapten applied epicutaneously induce tolerance. We examined epiderma l Langerhans cells at the site of contact with picryl chloride or oxaz olone in BALB/c and C57B1/6 mice with regard to their responding to ei ther subsensitizing or sensitizing doses of allergen. Subsensitizing d oses did not interfere with the membranous adenosine triphosphatase sy stem on Langerhans cells, known to relate to functional readiness of t he cell. Accordingly, on electron microscopy the ultrastructure of Lan gerhans cells was found to be like that in untreated skin. In contrast , sensitizing doses caused a significant depletion of adenosine tripho sphatase-positive Langerhans cells, and electron microscopy revealed m arked cellular activation of Langerhans cells, with enlarged nuclei an d increased numbers of mitochondria and Birbeck granules. Furthermore, subsensitizing doses induced tolerance regardless of whether Langerha ns cells were functionally intact or had their function blocked arbitr arily. Blocking was achieved either by preceding ultraviolet B irradia tion at the site of application or by painting of a sensitizer before painting another sensitizer on the same site. Moreover, not even surgi cal removal of the site within minutes after painting could prevent th e induction of tolerance. The data suggest that subsensitizing doses o f contact allergens painted on normal murine skin bypass involvement o f epidermal Langerhans cells.