Schwarz A, Grabbe S, Mahnke K, Riemann H, Luger T A, Wysocka M, Trinchieri G, Schwarz T
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University Münster, Germany.
J Invest Dermatol. 1998 Mar;110(3):272-6. doi: 10.1046/j.1523-1747.1998.00111.x.
Recent studies showed that injection of interleukin (IL)-12 prevents ultraviolet (UV) light mediated suppression of contact hypersensitivity and breaks UV-induced hapten specific tolerance. UV-mediated suppression can be adoptively transferred by injecting splenocytes from UV-irradiated mice; however, suppression is not transferable when donor mice are treated with IL-12 after UV-irradiation. This study was performed to elucidate the mechanisms by which IL-12 counteracts this immunosuppression. To characterize the cells transferring suppression, depletion studies were performed revealing that UV-induced suppression is transferred via CD8+ T cells. To investigate whether IL-12 counteracts UV-induced suppression by either inhibiting the development of CD8+ suppressor T cells or inducing CD4+ effector T cells, splenocytes from mice, which were IL-12 treated and sensitized through UV-exposed skin, were depleted from CD4+ T cells and transferred into naive mice that were subsequently sensitized. Whereas transfer of splenocytes from UV-irradiated mice inhibited sensitization of recipients, no inhibition was observed after transfer of splenocytes from UV-exposed and IL-12 treated mice. Recipients that received CD4 depleted spleen cells from UV-exposed and IL-12 treated donors, were still fully sensitizable. IL-12 also blocked transfer of UV-induced suppression when it was injected into UV-exposed donor animals at a time point when suppressor cells had already developed. CD4 depletion of such splenocytes did not result in a loss of the reconstitutive effect of IL-12. This suggests that IL-12 may break UV-induced tolerance not by inducing CD4+ effector T cells, but rather by inhibiting or inactivating suppressor T cells belonging to the CD8 subtype.
近期研究表明，注射白细胞介素（IL）-12可预防紫外线（UV）介导的接触性超敏反应抑制，并打破UV诱导的半抗原特异性耐受。UV介导的抑制作用可通过注射来自UV照射小鼠的脾细胞进行过继转移；然而，当供体小鼠在UV照射后用IL-12处理时，抑制作用则无法转移。本研究旨在阐明IL-12对抗这种免疫抑制的机制。为了表征转移抑制作用的细胞，进行了清除实验，结果显示UV诱导的抑制作用是通过CD8+T细胞转移的。为了研究IL-12是否通过抑制CD8+抑制性T细胞的发育或诱导CD4+效应性T细胞来对抗UV诱导的抑制作用，将经IL-12处理并通过UV照射皮肤致敏的小鼠的脾细胞中的CD4+T细胞清除后，转移至随后致敏的未致敏小鼠体内。虽然来自UV照射小鼠的脾细胞转移抑制了受体的致敏，但来自UV照射和IL-12处理小鼠的脾细胞转移后未观察到抑制作用。接受来自UV照射和IL-12处理供体的CD4清除脾细胞的受体仍可完全致敏。当在抑制性细胞已经发育的时间点将IL-12注射到UV照射的供体动物体内时，IL-12也阻断了UV诱导的抑制作用的转移。此类脾细胞的CD4清除并未导致IL-12的重建作用丧失。这表明IL-12可能不是通过诱导CD4+效应性T细胞来打破UV诱导的耐受，而是通过抑制或使属于CD8亚型的抑制性T细胞失活来实现的。
