Susceptibility to immunosuppression by ultraviolet B radiation in the mouse

Abstract

Irradiation with ultraviolet B (UVB; 290-320 nm) initiates systemic immunosuppression of contact hypersensitivity (CHS). UV dose-responses for suppression of CHS to trinitrochlorobenzene were established in 18 strains of inbred mice. Three phenotypes with significantly different susceptibilities to UV suppression were identified. The phenotypes were: high (HI) susceptibility, 50% suppression with 0.7-2.3 kJ/m2 UV (C57BL/6, C57BL/10, and C57L and NZB females); low (LO) susceptibility, 50% suppression with 9.6-12.3 kJ/m2 UV (BALB/c, AKR, SJL and NZW), and intermediate (INT) susceptibility, 50% suppression with 4.7-6.9 kJ/m2 UV (DBA/2, C57BR, C3H/HeJ, C3H/HeN, CBA/N and A/J). UV suppression 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, however, male mice (LO) were seven times less sensitive to UV suppression than NZB female mice (HI). Both sexes of (NZB x NZW)F1 and (NZW x NZB)F1 mice were HI, supporting dominance of HI over LO. Thus there are genetic factors and interacting sex-limited factors determining susceptibility to UV suppression. These findings may be of relevance to UV-related diseases such as photosensitive lupus and skin cancer.

Absence of p53-dependent apoptosis leads to UV radiation hypersensitivity, enhanced immunosuppression and cellular senescence

“…These results differ from those found in p53 -/-mice, which did not display increased susceptibility to UVBinduced immune suppression compared to wild-type mice. 22 Since it is known that different strains of mice exhibit different levels of susceptibility to UV-induced immune suppression, 43,44 it is possible that the strain of mice utilized in our study (C57BL/6 129/Sv mix) could explain the discrepancy between the results observed in p53 -/-and p53 R172P mice. However, this explanation is unlikely because the littermate controls in our study did not exhibit the same sensitivity as p53 R172P mice.…”

Genetic control of susceptibility to UV-induced immunosuppression by interacting quantitative trait loci

“…Gender was not a significant variable, in agreement with our previous observations. 4,5 The data was obtained in four separate experiments in which parental animals were also UV irradiated. In each of the four experiments, values for % suppression for parental BALB/c females and CB6F 1 males were within the range shown in Figure 1.…”

“…4,5 Single marker analysis: A genome-wide scan was carried out by regression of each marker on the transformed value for the phenotype. The regression included a 'blocking factor' for experiments one through four to account for experiment to experiment variation.…”

“…Phenotype for UV-induced immunosuppression was established, as previously published, 4,5 by quantitation of the systemic decrease in contact hypersensitivity response (CHS) after treatment with a standard dose of UV radiation. Briefly, backcross mice had their backs shaved with electric clippers, the ears covered with black electrical tape and were anesthetized with Nembutal (50 mg/kg) i/p and UV irradiated with a dose of 4.5 kJ/m 2 (15 min exposure) of UV from a bank of FS40 sunlamps.…”

“…3 We previously derived a genetic model for control of systemic susceptibility to UV-induced immunosuppression in inbred strains of mice. 4,5 We described a six-fold difference in UV dose required for generating 50% immunosuppression of contact hypersensitivity between mouse strains which was independent of pigmentation and independent of the innate ability to be contact sensitized in unirradiated animals. Using parental backcross and F 2 generation animals, derived from the parental strains BALB/c (low susceptibility to UV immunosuppression) and C57BL/6 (high susceptibility to UV immunosuppression), we demonstrated the action of three interacting but unlinked loci, two autosomal loci and an Xlinked locus.…”