A human-SCID mouse model for allergic immune response bacterial superantigen enhances skin inflammation and suppresses IgE production.
Chronic skin colonization with Staphylococcus aureus is a well-known feature in atopic dermatitis. The aim of this study was to develop a human-SCID mouse model to analyze the possible role of bacterial superantigens in human allergic immune responses under in vivo conditions. SCID mice were reconstituted with peripheral blood mononuclear cells (between 2 and 9 x 10(7) cells per mouse) from atopic dermatitis patients sensitized to house dust mite allergen (Der p). Total and Der p specific antibody production required the following conditions: (i) injection of Der p; (ii) presence of CD14+ antigen-presenting cells; and (iii) IL-4 as shown by the inhibitory effect of human soluble IL-4 receptor on immunoglobulin E production. This model was used to study the immunomodulatory effects of the superantigen staphylococcal enterotoxin B in comparison with Der p. In intraperitoneally reconstituted human-SCID mice, topical treatment was ineffective in inducing skin inflammation. Therefore, additionally to intraperitoneal transfer, peripheral blood mononuclear cells from atopic donors were also injected intradermally. Such reconstituted SCID mice were then exposed via the skin to either Der p, staphylococcal enterotoxin B, or a combination of both. Maximal effects on epidermal inflammation and dermal T cell infiltration were obtained with staphylococcal enterotoxin B and Der p. Staphylococcal enterotoxin B alone was less effective and Der p only stimulated dermal T cell infiltration. These findings support the hypothesis that bacterial superantigens can act as trigger factors in allergic skin inflammation.
Herz
U
U
Department of Clinical Chemistry, Virchow-Klinikum of the Humboldt-Universität, Berlin, Germany.
Schnoy
N
N
Borelli
S
S
Weigl
L
L
Käsbohrer
U
U
Daser
A
A
Wahn
U
U
Köttgen
E
E
Renz
H
H
D000287:Administration, Topical; D000818:Animals; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D039741:Antigens, Dermatophagoides; D001402:B-Lymphocytes / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000187:drug effects; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000637:transplantation; D018089:Superantigens / Q000276:immunology*
D000942:Antigens, Bacterial; D039741:Antigens, Dermatophagoides; D004768:Enterotoxins; D006023:Glycoproteins; D018089:Superantigens; D015847:Interleukin-4; D007073:Immunoglobulin E; C031818:enterotoxin B, staphylococcal