title: Keratinocyte-derived, CD80-mediated costimulation is associated with hapten-specific IgE production during contact hypersensitivity to TH1 haptens.
abstract: Background B7-1 transgenic mice exhibit exaggerated and persistent contact hypersensitivity responses compared with normal mice. Objective Because B7-1 and B7-2 deliver different costimulatory signals to T cells during antigen presentation, the purpose of this study was to compare B7-1 and B7-2 on keratinocytes and to compare their effects on contact hypersensitivity. Methods Contact hypersensitivity was studied in transgenic mice whose keratinocytes constitutively expressed B7-1, B7-2, or no costimulatory molecules (nontransgenic mice). Results B7-1 transgenic mice, and to a lesser extent B7-2 transgenic mice, developed exaggerated ear swelling responses after sensitization and challenge with haptens such as trinitrochlorobenzene or dinitrofluorobenzene. Ear swelling responses in B7-1 transgenic mice were characterized by the presence of markedly elevated inflammatory cytokine transcripts (IL-6, TNF-alpha, and lymphotoxin beta) as well as IL-10 compared with either B7-2 or nontransgenic mice. Hapten-specific IgE was detected by ELISA in B7-1 transgenic mice but not B7-2 transgenic or nontransgenic mice. Only B7-1 transgenic mice exhibited significant immediate type ear swelling responses to the hapten trinitrochlorobenzene. In addition, their sera can passively transfer cutaneous anaphylaxis to naive C57BL/6 mice, indicating that the hapten-specific IgE was relevant to the immediate ear swelling responses. Conclusion These data suggest that keratinocyte-derived costimulation mediated by B7-1 but not B7-2 results in the emergence of T H 2-lymphocyte immune responses to T H 1 haptens. Because human keratinocytes have been noted to express B7-1-like molecules in certain inflammatory skin diseases, this model may be important in understanding the pathophysiology of T H 2-lymphocyte-mediated skin diseases such as atopic dermatitis.
authors.affiliation: Department of Dermatology, University of Rochester School of Medicine, Rochester, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Burns
authors.forename: Irina
authors.initials: I
authors.lastname: Luzina
authors.forename: Adnan
authors.initials: A
authors.lastname: Nasir
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Haidaris
authors.forename: Richard K
authors.initials: RK
authors.lastname: Barth
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Gaspari
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D002722:Chlorobenzenes / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D004427:Ear Diseases / Q000276:immunology; D004487:Edema / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015603:Keratinocytes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D002722:Chlorobenzenes; D006241:Haptens; D008562:Membrane Glycoproteins; C036720:trichlorobenzene; D007073:Immunoglobulin E; D004139:Dinitrofluorobenzene