T-Lymphocyte Dependence of Psoriatic Pathology in Human Psoriatic Skin Grafted to SCID Mice

Abstract

Considerable indirect evidence suggests that T lymphocytes have a role in the pathogenesis of psoriasis. The goal of this study was to directly test the ability of T cells to maintain psoriasis pathology. Psoriatic skin was transplanted onto SCID mice, which were then injected with autologous T cells. T cells were cultured from either psoriatic skin lesions or peripheral blood and injected intradermally or intravenously. Control SCID mice transplanted with psoriasis grafts were not injected with T cells. After 10 wk, control psoriatic skin grafts not injected with T cells lost many of the features of psoriasis. Injection of peripheral blood T cells was not able to maintain these psoriatic features. In contrast, the injection of T cells derived from psoriatic skin was able to maintain the psoriatic phenotype. Psoriatic features that were maintained included epidermal thickness and labeling index and expression of HLA-DR, involucrin, and ICAM-1, as well as loss of expression of filaggrin. Injection of skin infiltrating T cells into skin of normal donors on SCID mice did not induce changes of psoriasis. The ability of T cells from lesional skin, but not peripheral blood, to maintain psoriasis suggests that psoriasis is mediated by an autoantigen reactive T cell, which is present at a higher frequency in the psoriatic lesion.

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 human skin-SCID mouse transplant model provides a means for investigating the pathophysiology of psoriasis (Gilhar et al, 1997;Nickoloff and WroneSmith, 1999;Wrone-Smith and Nickoloff, 1996). Based on the findings presented in this report, we suggest that the human skin-SCID mouse transplant model may also be of use in the assessment of potential antipsoriatic therapies.…”

“…The induction of normal skin proliferation after transplantation does not seem, therefore, to prevent the use of human skin-SCID mouse chimeras for the study of antipsoriatic agents, although it does complicate the issue. This same phenomena also makes it more difficult to interpret findings related to induction of a psoriatic phenotype in nonlesional skin (Gilhar et al, 1997;Nickoloff and Wrone-Smith, 1999;Wrone-Smith and Nickoloff, 1996).…”

“…Transplantation of human skin onto immunocompromised mice (either congenitally athymic [nude] mice or severe combined immunodeficiency [SCID] mice) provides another approach to the study of psoriasis (Baker et al, 1992;Gilhar et al, 1997;Krueger, 1975;Krueger et al, 1981;Nickoloff et al, 1995;Nickoloff and Wrone-Smith, 1999;Wrone-Smith and Nickoloff, 1996). Using this approach, at least some of the phenotypic features of the disease (ie, epidermal thickening, extensive rete peg formation, and presence of inflammatory cells) are maintained for an extended period in the transplanted skin (Nickoloff et al, 1995).…”

“…Using this approach, at least some of the phenotypic features of the disease (ie, epidermal thickening, extensive rete peg formation, and presence of inflammatory cells) are maintained for an extended period in the transplanted skin (Nickoloff et al, 1995). Although other characteristics of the psoriatic phenotype are lost over time, their loss seems to be retarded by co-injection of immune cells from psoriatic patients (Gilhar et al, 1997). Recent studies suggest that co-injection of circulating CD4-positive lymphocytes from psoriatic patients not only preserves psoriatic features in lesional skin, but also induces expression of the psoriatic phenotype in nonlesional skin (Nickoloff and Wrone-Smith, 1999;Wrone-Smith and Nickoloff, 1996).…”

CCR3-Blocking Antibody Inhibits Allergen-Induced Eosinophil Recruitment in Human Skin Xenografts from Allergic Patients

“…These mice have a defect in antigen receptors on the T and B lymphocytes and can be reconstituted with a functional human immune system (Mosier et al, 1988). The model of SCID mice grafted with skin alone (Christofidou-Solomidou et al, 1996, 1997bJuhasz et al, 1993;Nickoloff et al, 1995;Yan et al, 1993) or with peripheral blood mononuclear cells (PBMC) has been previously extensively used in the field of skin diseases (Christofidou-Solomidou et al, 1997a;Gilhar et al, 1997) and to study different types of T cell-mediated cutaneous inflammation (Petzelbauer et al, 1996;Tsicopoulos et al, 1998) and graft rejection (Murray et al, 1994;Sultan et al, 1997) but never as a model of allergic reaction. In the present study, intradermal injection of allergen in SCID mice xenografted with human skin and autologous (PBMC) from the same allergic donors reproduced the features of the human allergen-induced LPR.…”