Characterization of the altered cutaneous reactivity of transgenic mice whose keratinocytes overexpress B7-1.
B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs that prevents the induction of T-cell clonal anergy and induces IL-2 production during antigen presentation. Tg mice whose epidermal KC overexpress B7-1 exhibit exaggerated and persistent CHS to a variety of haptens that lasts up to 8 weeks after hapten challenge. These Tg mice also exhibit significantly enhanced ear-swelling responses to irritants that are not persistent. Exaggerated CHS was not reflected in the draining lymph node. T-lymphocyte proliferative responses after sensitization and local challenge with haptens, as there were no significant differences between the B7-1 Tg and the NTg mice. However, RT-PCR analysis of mouse ear skin at the hapten challenge site indicated that B7-1 Tg mice had an alteration in the kinetics of in situ lymphokine transcripts compared to NTg mice: IFN-gamma transcripts were first detectable in Tg mouse skin at 2 weeks versus 24 h for NTg mice. RNase protection assays to detect inflammatory cytokine transcripts at hapten application sites indicated that B7-1 Tg mice responded to hapten application with increased TNF-alpha, IL-6, and TNF-beta transcripts compared to NTg mice. Thus, hapten-induced ear swelling in these Tg mice may be mediated by enhanced inflammatory cytokines during the early phase (1-14 days). IFN-gamma-producing lymphocytes may be responsible for the late phase of the ear-swelling response (14-42 days). These data indicate that B7-1 overexpression by KC in mouse skin directly or indirectly affects the nature of cutaneous inflammation induced by haptens and irritants.
Gaspari
A A
AA
Department of Dermatology, University of Rochester School of Medicine and Dentistry, New York 14642, USA. AGPI@db3.cc.Rochester.edu
Burns
R P
RP
Kondo
S
S
Nasir
A
A
Kurup
A
A
Mlodynia
D
D
Sauder
D
D
Barth
R K
RK
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D001483:Base Sequence; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D006241:Haptens / Q000008:administration & dosage; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D018122:B7-1 Antigen; D016207:Cytokines; D017931:DNA Primers; D006241:Haptens; D018836:Inflammation Mediators