THE ACTION SPECTRA FOR UV-INDUCED SUPPRESSION OF MLR AND MECLR SHOW THAT IMMUNOSUPPRESSION IS MEDIATED BY DNA-DAMAGE

Ultraviolet-B (UVB, 280-320 nm) radiation can promote the induction of skin cancer by two mechanisms: damage of epidermal DNA and suppressio n of the immune system, allowing the developing tumor to escape immune surveillance. The mixed lymphocyte reaction (MLR) and the mixed epide rmal cell lymphocyte reaction (MECLR) are commonly used methods to stu dy the immunosuppressive effects of UVB radiation. To obtain a better understanding of the mechanism by which UVB radiation decreases the al loactivating capacity of in vitro-irradiated cells, action spectra for the MLR and MECLR were determined. Suspensions of peripheral blood mo nonuclear cells or epidermal cells were irradiated with monochromatic light of 254, 297, 302 or 312 nm and used as stimulator cells in the M LR or MECLR. Using dose-response curves for each wavelength, the actio n spectra were calculated. Both MLR and MECLR action spectra had a max imum at 254 nm and a relative sensitivity at 312 nm that was a thousan d times lower than at 254 nm. Strikingly, the action spectra correspon ded very closely to the action spectra that were found by Matsunaga et al. (Photochem. Photobiol. 54, 403-410, 1991) for the induction of th ymine dimers and (6-4)photoproducts in irradiated calf thymus DNA solu tions, strongly suggesting that the UV-induced abrogation of the MLR a nd MECLR responses is mediated by UV-induced DNA damage. Furthermore, the action spectra for the MLR and MECLR were similar, suggesting that they share a common mechanism for UV-induced suppression.