Hart P H, Grimbaldeston M A, Swift G J, Sedgwick J D, Körner H, Finlay-Jones J J
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide, Australia.
Eur J Immunol. 1998 Sep;28(9):2893-901. doi: 10.1002/(SICI)1521-4141(199809)28:09<2893::AID-IMMU2893>3.0.CO;2-U.
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.
紫外线辐射产生免疫抑制作用的机制存在争议，但越来越多的证据表明，如果将致敏抗原应用于受照射部位与未受照射部位，紫外线B（UVB）诱导的针对该致敏抗原的免疫反应抑制过程是不同的。与此相符的是，我们最近的观察结果（Hart等人，《实验医学杂志》，1998年。187: 2045 - 2053）表明，皮肤肥大细胞的数量决定了不同小鼠品系对UVB诱导的全身而非局部免疫抑制的敏感程度。分别使用暴露于低剂量和高剂量UVB的C57BL/6和BALB/c小鼠，在存在多克隆抗TNF抗体的情况下，我们发现TNF作为介质直接参与了UVB对局部免疫反应的抑制作用。为了确定TNF是否通过改变皮肤肥大细胞的数量间接调节UVB诱导的全身免疫调节，通过视频图像分析对缺乏TNF或TNF受体的基因靶向小鼠（p55/p75 - / - 小鼠）中的皮肤肥大细胞数量进行了定量。这些小鼠中皮肤肥大细胞数量的减少与UVB引起的全身免疫抑制易感性降低相关。我们推测TNF是一种通过尚未明确的机制控制皮肤肥大细胞数量的分子。然而，正是肥大细胞在UVB诱导脱颗粒时释放的介质（其中不包括TNF）直接发出与全身免疫抑制相关的抑制信号。
