T-lymphocyte dependence of psoriatic pathology in human psoriatic skin grafted to SCID mice.
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.
Gilhar
A
A
Skin Research Laboratory, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
David
M
M
Ullmann
Y
Y
Berkutski
T
T
Kalish
R S
RS
D019264:Adoptive Transfer; D000818:Animals; D017690:Cell Transplantation; D004195:Disease Models, Animal; D000091344:Filaggrin Proteins; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D011498:Protein Precursors / Q000096:biosynthesis; D011565:Psoriasis / Q000235:genetics / Q000473:pathology*; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000473:pathology*
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006684:HLA-DR Antigens; D011498:Protein Precursors; D018799:Intercellular Adhesion Molecule-1; C032253:involucrin