IN-VITRO MODEL FOR CONTACT SENSITIZATION .1. STIMULATORY CAPACITIES OF HUMAN BLOOD-DERIVED DENDRITIC CELLS AND THEIR PHENOTYPICAL ALTERATIONS IN THE PRESENCE OF CONTACT SENSITIZERS

Dendritic cells (DC) are highly specialized antigen-presenting cells ( APC) located in many non-lymphoid tissues and a specialized form of DC -the Langerhans cell (LC)-is found in the skin. The functionality of L C as APC is crucial for the induction of an allergic contact dermatiti s. For a long time LC research has been hampered by the limiting numbe rs of functionally active LC that could be isolated from human skin. T he addition of GM-CSF and IL-4 to the non-adherent fraction of mononuc lear cells from peripheral blood generated a large amount of CD1a(+) H LA-DR+ DC. These in vitro-generated DC exhibited the morphology, pheno type and autologous T-lymphocyte stimulating capacity of the human DC/ LC system. We had tested phenotypical alterations of in vitro-generate d DC under the influence of subtoxic concentrations of different chemi cals and contact sensitizers. In vitro stimulation with the contact se nsitizers urushiol, primin, C10- and C11-primin analogues, alantolacto ne, isoalantolactone and NiSO4 resulted in a decrease of HLA-DR expres sion on the surface of these cells if the incubation period did not ex ceed 3 hr. Incubation with irritants like sodium lauryl sulfate (SLS) and benzalkonium chloride did not change or increase the HLA-DR surfac e expression under these conditions. With regard to the adhesion molec ule ICAM-1, there was no clear difference between irritants and contac t sensitizers. But based on the alteration of HLA-DR expression of den dritic cells under short-term exposure conditions, there was a clear-c ut difference between irritants and contact sensitizers. In summary, t his system can be used to discriminate between contact sensitizers and irritants. (C) 1997 Published by Elsevier Science Ltd.