Aa. Gaspari et al., CHARACTERIZATION OF THE ALTERED CUTANEOUS REACTIVITY OF TRANSGENIC MICE WHOSE KERATINOCYTES OVEREXPRESS B7-1, Clinical immunology and immunopathology, 86(3), 1998, pp. 259-270
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.