Rôle of DNA damage in local suppression of contact hypersensitivity in mice by UV radiation.
Exposure of mice to UVB radiation down-regulates the induction of contact hypersensitivity (CHS) responses to haptens applied to the site of irradiation. Concomittantly, the activity of antigen-presenting cells (APC) in the draining lymph nodes is decreased, and T lymphocytes that suppress the induction of CHS are induced. We assessed the rôle of DNA damage in modulation of the CHS response by UV irradiation by applying liposomes containing T4 endonuclease V (T4N5) to the UV-irradiated skin. Liposomal T4N5, which increases the rate of repair of cyclobutyl pyrimidine dimers (CPD) in DNA, prevented the reduction in the CHS response, the impairement in APC function, and the induction of transferrable immune suppression. Liposomes containing heat-inactivated T4N5 did not restore immune responsiveness. In this model, hapten-bearing APC from unirradiated mice also fail to induce CHS upon injection into UV-irradiated recipients. This systemic effect of UV irradiation on APC function was also prevented by application of liposomes containing active, but not inactive, T4N5. These studies support the hypothesis that DNA damage is an essential initiator of one or more steps leading to impaired immune responsiveness after UV irradiation. They further imply that the release of cytokines that modulate APC function after UV irradiation is triggered by DNA damage.
Kripke
M L
ML
Department of Immunology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Cox
P A
PA
Bucana
C
C
Vink
A A
AA
Alas
L
L
Yarosh
D B
DB
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D004249:DNA Damage; D003877:Dermatitis, Contact / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006241:Haptens; D051379:Mice; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology; D014466:Ultraviolet Rays; D014467:Ultraviolet Therapy
D006241:Haptens