Psoriasis is mediated by a cutaneous defect triggered by activated immunocytes: Induction of psoriasis by cells with natural killer receptors

This study was performed to ask whether psoriasis is a unique pathologic response of epidermis of psoriatic patients, or cells with natural killer receptors can induce psoriatic changes in skin from nonpsoriatic donors. Human nonlesional skin from five psoriatics, as well as from seven nonpsoriatics was grafted on to beige-SCID mice. Lymphocyte lines with natural killer activity, and mixed natural killer, natural killer T cell phenotype, were generated by culture of peripheral blood mononuclear cells from both psoriatic, and normal donors, in 100 U interleukin-2 per ml for 14 d. Natural killer cells were injected into the human skin grafts, and the grafts were harvested after 4 wk. Injection of natural killer cells from psoriatic donors into autologous nonlesional psoriatic skin resulted in classic psoriasis histology with a significant increase in epidermal thickness, and proliferation, as well as expression of epidermal human leukocyte antigen DR, intercellular adhesion molecule-1, CD1d, and K-16. Superantigen stimulation was not necessary. In contrast, injection of natural killer cells from normal donors into autologous normal skin did not induce the histology of psoriasis, but that of psoriasiform dermatitis. This is a nonspecific reaction pattern. These grafts also exhibited a significant increase in epidermal thickness, and proliferation. Differences from psoriasis included mild epidermal edema (spongiosis), hypergranulosis, irregular elongation of rete ridges, and lack of thinning of the suprapapillary plate. Injection of allogeneic natural killer cells into grafts also resulted in psoriasiform dermatitis, regardless of the source of natural killer cells, or skin. Psoriasis induction by cells with natural killer receptors appears to be dependent upon the source of skin. This suggests that psoriasis results from a cutaneous defect that is triggered by an autoimmune activation.