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 ''prof essional'' APCs that prevents the induction of T-cell clonal anergy an d induces IL-2 production during antigen presentation. Tg mice whose e pidermal 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 respon ses to irritants that are not persistent. Exaggerated CHS was not refl ected 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 indic ated that B7-1 Tg mice had an alteration in the kinetics of in situ ly mphokine 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 a t hapten application sites indicated that B7-1 Tg mice responded to ha pten application with increased TNF-alpha, IL-6, and TNF-beta transcri pts compared to NTg mice. Thus, hapten-induced ear swelling in these T g mice may be mediated by enhanced inflammatory cytokines during the e arly phase (1-14 days). IFN-gamma-producing lymphocytes may be respons ible for the late phase of the ear-swelling response (14-42 days). The se 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. (C) 1998 Academic Press.