The SCID-hu Skin mouse as a model to investigate selective chemokine mediated homing of human T-lymphocytes to the skin in vivo.
Here we report the establishment of an in vivo mouse model that allows monitoring of human T cell migration into human skin. This model is based on the use of severe combined immunodeficiency (SCID) mice transplanted with human skin (SCID-hu Skin mice). Adoptively transferred human T helper (Th)2 cells obtained from atopic dermatitis skin lesions or peripheral blood T cells selectively migrate to the human skin grafts of these SCID mice in response to defined chemokines locally injected in the human skin grafts. Homing of human T cells into the human skin on SCID-hu Skin mice is a specific process since it only occurs in response to chemokine ligands that are specific for the chemokine receptors expressed on the migrating T cells. This mechanistic model allows analysis of the relevant steps involved in human T-lymphocyte migration into inflamed skin. In addition, it is successfully used for preclinical testing of drug candidates that are highly selective for human target molecules associated with the different steps of T cell migration in an environment that resembles the physiologic or pathologic conditions occurring in man.
Carballido
José M
JM
Novartis Research Institute, Brunner Strasse 59, Vienna A-1235, Austria.
Biedermann
Tilo
T
Schwärzler
Christoph
C
de Vries
Jan E
JE
D000818:Animals; D018925:Chemokines / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D006801:Humans; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D023421:Models, Animal; D019707:Receptors, Chemokine / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D012867:Skin / Q000276:immunology*; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D018925:Chemokines; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing