Ultraviolet B-Exposed and Soluble Factor-Pre-Incubated Epidermal Langerhans Cells Fail to Induce Contact Hypersensitivity and Promote DNP-Specific Tolerance

Abstract

Acute low-dose ultraviolet B (UVB) radiation impairs the induction of contact hypersensitivity (CH) and induces tolerance in UVB-susceptible strains of mice when dinitrofluorobenzene (DNFB) is applied to an irradiated skin surface. We are interested in learning the cellular and molecular bases for the existence of UVB susceptibility in certain strains of mice. CH was induced by subcutaneous injections into naive syngeneic C57BL/6 and BALB/c mice of dinitrophenyl (DNP)-derivatized Thy-1(+)-depleted epidermal cells enriched for Ia+ cells (LC/DNP, 2 x 10(4) cells per mouse). Tolerance was detected by applying 185 microg of DNFB epicutaneously to mice treated 2 wk earlier with a putative tolerating regimen and testing CH expression. We found that LC/DNP obtained from C57BL/6 skin 2 h after UVB irradiation (400 J per m2) failed to induce CH and induced DNP-specific tolerance instead; by contrast, similar cells obtained from same or even higher dose (400 J per m2 and 1200 J per m2) UVB-exposed BALB/c skin induced vigorous CH, and no tolerance was detected. In both C57BL/6 and BALB/c mice, Ia+-depleted EC/DNP neither sensitized naive syngeneic mice nor induced tolerance. LC/DNP prepared from unirradiated trunk skin of either C57BL/6 or BALB/c mice and pre-incubated in vitro for 2 h with cis-UCA, TNF-alpha, or IL-10 failed to induce intense CH; instead, all induced DNP-specific tolerance. Pre-incubation of similar LCs with alpha-MSH in vitro for 2 h also failed to induce CH but did not cause tolerance. Thus, single low-dose UVB irradiation alters the immunogenic and tolerogenic potentials of LCs only in UVB-susceptible mice; by contrast, pre-treatment of LCs with UVB-dependent soluble factors can achieve effects similar to UVB irradiation in both UVB-susceptible and -resistant strains of mice. These findings demonstrate that UVB susceptibility in mice may be determined by the production of UVB-dependent soluble factors within UVB-irradiated skin.