TNF MODULATES SUSCEPTIBILITY TO UVB-INDUCED SYSTEMIC IMMUNOMODULATIONIN MICE BY EFFECTS ON DERMAL MAST-CELL PREVALENCE

The mechanisms by which UV radiation is immunosuppressive are controve rsial, but there is growing evidence that processes of UVB-induced sup pression of the immune response towards a sensitizing antigen are diff erent if this antigen is applied to irradiated compared with non-irrad iated sites. Consistent with this is our recent observation (Hart et a l., J. Exp. Med. 1998. 187: 2045-2053) that the prevalence of dermal m ast cells determines the extent of susceptibility of different mouse s trains to UVB-induced systemic, but not local, immunosuppression. Usin g C57BL/6 and BALB/c mice exposed to low and high doses of UVB, respec tively, in the presence of a polyclonal anti-TNF antibody, we found th at 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 d ermal mast cells, dermal mast cell numbers in gene-targeted mice defic ient in TNF or TNF receptors (p55/p75(-/-) mice) were quantified by vi deo image analysis. A reduced dermal mast cell prevalence in these mic e correlated with decreased susceptibility for systemic immunosuppress ion caused by UVB. We hypothesize that TNF is one molecule that contro ls dermal mast cell prevalence by as yet unknown mechanisms. However, it is the mediators released from mast cells upon UVB-induced degranul ation, which do not include TNF, that directly signal suppressive even ts relevant to systemic immunosuppression.