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Publication : Characterization of the altered cutaneous reactivity of transgenic mice whose keratinocytes overexpress B7-1.

First Author  Gaspari AA Year  1998
Journal  Clin Immunol Immunopathol Volume  86
Issue  3 Pages  259-70
PubMed ID  9557159 Mgi Jnum  J:46917
Mgi Id  MGI:1202232 Doi  10.1006/clin.1997.4491
Citation  Gaspari AA, et al. (1998) Characterization of the altered cutaneous reactivity of transgenic mice whose keratinocytes overexpress B7-1. Clin Immunol Immunopathol 86(3):259-70
abstractText  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.
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