Accumulating evidence has emphasized the importance of immunocompetent cells in determining the psoriatic phenotype. We have investigated the effect of 1alpha,25-dihydroxycholecalciferol, the naturally occurring active form of
vitamin D3,
cyclosporine A, and
interleukin-10 on the phenotype of human psoriatic skin xenotransplants. First, psoriatic skin transplants were injected with either 1alpha,25-dihydroxy-
cholecalciferol,
cyclosporine A, or
interleukin-10. Second, we determined the ability of autologous lymphocytes, activated in vitro using
staphylococcal enterotoxin B and
interleukin-2 and then exposed to either 1alpha, 25-dihydroxycholecalciferol or
cyclosporine A, to induce psoriatic lesions if they were injected into the dermis of uninvolved skin grafts. We found that
injections into transplanted psoriatic plaques of either 1alpha,25-dihydroxycholecalciferol or
cyclosporine A, but not
interleukin-10, resulted in a consistent reduction in the clinical and histologic score of
psoriasis with remission towards uninvolved psoriatic skin. Injection of activated immunocytes into symptomless psoriatic skin grafts, changed the grafts towards plaque-type
psoriasis with silvery scale,
parakeratosis, elongated rete pegs, acanthosis, and dermal angiogenic reaction. In contrast, if activated immunocytes were exposed to 1alpha, 25-dihydroxycholecalciferol or
cyclosporine A prior to injection, only minimal changes occurred. It was determined that neither
staphylococcal enterotoxin B and
interleukin-2 activation by itself, nor the drugs investigated, changed the CD4/CD8 ratio of activated (CD25 + ) cells. Our results are consistent with the hypothesis that
psoriasis may be induced by activated T lymphocytes, and indicate that novel
immunomodulatory drugs can serve to inhibit the pathogenetic ability of immunocytes in
psoriasis.