A novel T cell receptor transgenic animal model of seborrheic dermatitis-like skin disease.
We have characterized a novel animal model of the common inflammatory skin disease seborrheic dermatitis (SD) that involves the expression of the self-specific 2C transgenic T cell receptor on the DBA/2 genetic background. Opportunistic fungal pathogens are present in the primary histological lesions and severe disease can be mitigated by the administration of fluconazole, demonstrating a role for infection in disease pathogenesis. Spontaneous disease convalescence occurs at 70-90 d of age and is preceded by an expansion of CD4+ T cells that partially restores the T cell lymphopenia that occurs in these animals. The adoptive transfer of syngeneic CD4+ T cells into pre-diseased DBA/2 2C mice completely abrogates the development of cutaneous disease. The pattern of disease inheritance in DBA/2 backcrosses suggests that one, or a closely linked group of genes, may control disease penetrance. Bone marrow reconstitution experiments demonstrated that the DBA/2 susceptibility factor(s) governing disease penetrance is likely non-hematopoietic since bone marrow from disease-resistant 2C mice can adoptively transfer the full disease phenotype to non-transgenic DBA/2 animals. This model implicates fungal organisms and CD4+ T cell lymphopenia in the development of a SD-like condition and, as such, may mimic the development of SD in acquired immunodeficiency syndrome.
Oble
Darryl A
DA
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Collett
Elisabeth
E
Hsieh
Mindy
M
Ambjørn
Malene
M
Law
Jennie
J
Dutz
Jan
J
Teh
Hung-Sia
HS
D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D012628:Dermatitis, Seborrheic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D016867:Immunocompromised Host / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009181:Mycoses / Q000276:immunology / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D012741:Sexual Maturation
D000941:Antigens; D011948:Receptors, Antigen, T-Cell