TNF modulates susceptibility to UVB-induced systemic immunomodulation in mice by effects on dermal mast cell...

The mechanisms by which UV radiation is immunosuppressive are controversial, but there is growing evidence that processes of UVB-induced suppression of the immune response towards a sensitizing antigen are different if this antigen is applied to irradiated compared with non-irradiated sites. Consistent with this is our recent observation (Hart et al., J. Exp. Med. 1998. 187: 2045-2053) that the prevalence of dermal mast cells determines the extent of susceptibility of different mouse strains to UVB-induced systemic, but not local, immunosuppression. Using C57BL/6 and BALB/c mice exposed to low and high doses of UVB, respectively, in the presence of a polyclonal anti-TNF antibody, we found that TNF is directly involved as a mediator in the suppression by UVB of local immune responses. To determine whether TNF indirectly regulates UVB-induced systemic immunomodulation by altering the prevalence of dermal mast cells, dermal mast cell numbers in gene-targeted mice deficient in TNF or TNF receptors (p55/p75-/- mice) were quantified by video image analysis. A reduced dermal mast cell prevalence in these mice correlated with decreased susceptibility for systemic immunosuppression caused by UVB. We hypothesize that TNF is one molecule that controls dermal mast cell prevalence by as yet unknown mechanisms. However, it is the mediators released from mast cells upon UVB-induced degranulation, which do not include TNF, that directly signal suppressive events relevant to systemic immunosuppression.