Immunogene#cs 39: 29-39, 1994 ll lllllllO- genetics © Springer-Verlag 1994 Susceptibility to immunosuppression by ultraviolet B radiation in the mouse Frances P. Noonanl, Harold A. Hoffman 2 Department of Dermatology, The George Washington University SchooI of Medicine, Ross Hall, Room 110, 2300 Eye St., NW, Washington, DC 20 037, USA 2 Animal Genetic Systems, Inc., 335 Paint Branch Dr., College Park, MD 20742, USA Received June 16, 1993/Revised version received July 14, 1993 Abstract. Irradiation with ultraviolet B (UVB; 290- 320 nm) initiates systemic immunosuppression of con- tact hypersensitivity (CHS). UV dose-responses for suppression of CHS to trinitrochlorobenzene were es- tablished in 18 strains of inbred mice. Three pheno- types with significantly different susceptibilities to UV suppression were identified. The phenotypes were: high (HI) susceptibility, 50% suppression with 0.7- 2.3 kJ/m 2 UV (C57BL/6, C57BL/10, and C57L and NZB females); low (LO) susceptibility, 50% suppres- sion with 9.6-12.3 kJ/m 2 UV (BALB/c, AKR, SJL and NZW), and intermediate (INT) susceptibility, 50% sup- pression with 4.7-6.9 kJ/m2 UV (DBA/2, C57BR, C3H/HeJ, C3H/HeN, CBA/N and A/J). UV suppres- sion was not correlated with skin pigmentation or with the magnitude of the CHS response in non-irradiated animals. Major histocompatibility complex (MHC) haplotype was not correlated with UV suppression in MHC congenic strains B10.D2/oSnJ, B10.D2/nSnJ, B10.BR/SgSnJ, and A.BY/SnJ. There were no sex differences in UV suppression in BALB/c, C57BL/6, or NZW animals. In the autoimmune NZB strain, how- ever, male mice (LO) were seven times less sensitive to UV suppression than NZB female mice (HI). Both sexes of (NZB × NZW)F1 and (NZW × NZB)F1 mice were HI, supporting dominance of HI over LO. Thus there are genetic factors and interacting sex-limit- ed factors determining susceptibility to UV suppres- sion. These findings may be of relevance to UV-related diseases such as photosensitive lupus and skin cancer. Introduction Irradiation of mice with ultraviolet B (UVB; 290- 320 nm) initiates a suppression of delayed-type hyper- sensitivity (DTH) and contact hypersensitivity (CHS) responses (Giannini 1986; Howie et al. 1986; Mottram et al. 1988; Noonan et al. 1981a; Streilein and Berg- stresser 1988; Yasumoto et al. 1987) which is both dose and wavelength dependent (De Fabo and Noonan 1983; Noonan et al. 1981 a). Immunosuppression occurs with biologically relevant doses of UVB which are readily available from natural sunlight (De Fabo et al. 1990). Suppression is a systemic event (Noonan et al. 1981 a), the UV dose-response being the same if an antigen is applied either to a UV-irradiated or to a non-irradiated site on a UV-treated animal (Noonan and De Fabo 1990). Suppression of CHS responses in humans by prior exposure to UVB has been reported, supporting the idea that this mechanism is relevant to human health (Cooper et al. 1992; Hersey et al. 1983; Kalimo et al. 1983; Vermeer et al. 1991). We have previously found a major difference in susceptibility to UVB suppression between mouse strains, BALB/c mice requiring nearly six times more UV than C57BL/6 mice for 50% sup- pression of CHS (Noonan and De Fabo 1990). Because of the potential role of UVB-induced immune suppres- sion in modulation of the immune response to en- vironmental antigens and in UV-related diseases, e.g., skin cancer (Daynes and Spellman 1977; De Fabo and Kripke 1979; De Fabo and Kripke 1980; Fisher and Kripke 1977; Fisher and Kripke 1982), we have inves- tigated further the differences in susceptibility to UV suppression between inbred mouse strains as an initial step in addressing the question of genetic control of this trait. Correspondence to: E R Noonan.