Anti-CD11a ameliorates disease in the human psoriatic skin-SCID mouse transplant model: Comparison of antibody to CD11a with cyclosporin A and clobetasol propionate

The present study assesses the applicability of human skin-SCID (severe com bined immunodeficiency) mouse chimeras in testing antipsoriatic therapeutic s. Three agents were examined: (1) a monoclonal antibody to the alpha subun it of leukocyte function associated antigen-1 integrin (CD11a); (2) Cyclosp orin A; and (3) clobetasol propionate (Temovate), a potent topical corticos teroid used clinically in the treatment of psoriasis. Skin transplanted to SCID mice from normal human volunteers or from psoriatic lesional skin was allowed to heal for 3 to 5 weeks before application of test reagents. Durin g this period, psoriatic skin, which was 3.8-fold thicker than the correspo nding normal skin before transplantation, maintained its phenotype (ie, inc reased epidermal thickness, rete ridges with blunted ends, and intralesiona l presence of T lymphocytes). Transplanted normal human skin, however, unde rwent a hyperplastic response during this period, resulting in a 2.4-fold i ncrease in epidermal thickness. After the healing period, animals transplan ted with normal or psoriatic skin were treated for 14 days by daily intrape ritoneal injection of either Cyclosporin A or a monoclonal antibody to huma n CD11a, or by topical application of clobetasol propionate. At the end of the treatment period, the mice were killed and the tissue evaluated morphom etrically for changes in epidermal thickness and immunohistologically for t he presence of T lymphocytes. Both Cyclosporin A and anti-CD11a reduced the epidermal thickness of transplanted psoriatic skin, whereas neither reagen t significantly reduced the thickness of transplanted normal skin. T lympho cytes were detected in the skin from treated animals; there did not seem to be any reduction in the number of T lymphocytes. Clobetasol propionate red uced the epidermal thickness of both normal and psoriatic skin. These data indicate that, in this model, therapies directed against pathophysiologic m echanisms that contribute to psoriasis can be distinguished from treatments that block epidermal hyperplasia occurring as a consequence of xenograftin g. Our observations provide evidence for the activity of anti-CD11a in an a nimal model of human psoriasis.