DIFFERENTIAL SUPPRESSION OF THE HUMAN MIXED EPIDERMAL-CELL LYMPHOCYTE-REACTION (MECLR) AND MIXED LYMPHOCYTE-REACTION (MLR) BY CIS-UROCANIC ACID

Cis-urocanic acid (UCA), formed in the stratum corneum by UV irradiati on of trans-UCA has been proposed as a mediator of UV-induced immunosu ppression in the skin, In this study, we examined the in vitro effect of cis-UCA (6-100 mu g/mL) on the human mixed lymphocyte reaction (MLR ) and the mixed epidermal cell lymphocyte reaction (MECLR), Addition o f cis-UCA (purified or in a mixture with trans-UCA) did not affect the MLR but was able to induce a 20% suppression of the MECLR responses, Because this effect of cis-UCA on the MECLR was not as strong as could be expected from previous in vivo results, we designed a set of exper iments in order to enhance the in vitro immunosuppressive capacity of cis-UCA. Firstly, we preincubated epidermal cells with UCA (50 mu g/mL ) for 3 or 6 days before culture in the MECLR because in vivo repeated UV exposure can lead to a photostationary state, where cis-UCA may be present for several weeks, This pretreatment with cis-UCA resulted in a maximal decrease of the MECLR responses of 27%, whereas trans-UCA h ad no effect, Secondly, we investigated whether UVB irradiation of epi dermal cells could make cells more sensitive to cis-UCA, However, addi tion of trans- or cis-UCA did not potentiate the reduced alloactivatin g capacity of UVB-irradiated cells, Finally, we examined the possibili ty of a synergistic effect of cis-UCA with histamine. Addition of hist amine suppressed the MLR and MECLR responses, but neither cis- nor tra ns-UCA were able to modulate this decrease, We conclude that cis-UCA c an partly downregulate the human MECLR but not the MLR, The mechanism involved in this differential downregulation is not known, In this res pect it is striking that cis-UCA does not potentiate the UVB- or hista mine-induced suppression of the MECLR.