Differential effects of a monoclonal antibody to cis-urocanic acid on the suppression of delayed and contact hypersensitivity following ultraviolet irradiation.
Urocanic acid (UCA) occurs naturally in the stratum corneum of the skin as the trans-isomer and, upon exposure to UVB radiation, converts to cis-UCA. It has been proposed that trans-UCA is the photoreceptor for and, following its isomerization to cis-UCA, a mediator of the suppressive effects of UVB irradiation on systemic T cell-mediated immune responses, such as contact hypersensitivity (CH) and delayed-type hypersensitivity (DTH). To address this question directly, we studied the consequence of deleting the in vivo function of cis-UCA on systemic suppression of CH and DTH, by injecting mice with a anti-cis-UCA mAb several hours before exposure to UVB radiation. We found that while DTH responses were completely restored, the anti-cis-UCA Ab had no effect on UV-induced immunosuppression of the CH response, even though suppressor cell formation was inhibited in both cases. Further, the kinetics of IL-10 expression in the skin of irradiated mice injected with the anti-cis-UCA mAb was altered and the diminished APC function of spleen-adherent cells from UVB-irradiated mice was totally reversed by the Ab. These findings suggest that cis-UCA acts as a mediator for some but not all of the systemic suppressive effects of UVB irradiation. They also suggest that cis-UCA may act indirectly via IL-10 to modulate immune function.
Moodycliffe
A M
AM
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Bucana
C D
CD
Kripke
M L
ML
Norval
M
M
Ullrich
S E
SE
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000502:physiology; D007536:Isomerism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010081:Oxazolone / Q000276:immunology; D012756:Sheep / Q000097:blood; D015398:Signal Transduction / Q000528:radiation effects*; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D016753:Interleukin-10; D010081:Oxazolone; D014560:Urocanic Acid