Ullrich S E, Pride M W, Moodycliffe A M
Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Immunology. 1998 Jul;94(3):417-23. doi: 10.1046/j.1365-2567.1998.00530.x.
Although almost all of the energy contained within the ultraviolet (UV) wavelengths of solar radiation is absorbed within the epidermis and upper layers of the dermis, UV irradiation can suppress the immune response to antigens introduced at distant, non-irradiated body sites. The production of immune modulatory cytokines, such as interleukin-10 (IL-10), by UV-irradiated keratinocytes and its effect on T helper type 1 (Th1)/Th2-cell balance are thought to play a major role in the induction of systemic immune suppression. Because it is suggested that costimulatory molecules, such as CD80 and CD86, differentially stimulate Th1 and Th2 cells we wished to investigate the role of these costimulatory molecules in the activation of immune suppression. We injected UV-irradiated mice with monoclonal antibodies to CD80 and CD86 and asked what effect, if any, this would have on UV-induced immune suppression. Anti-CD86, but not anti-CD80 or control rat IgG, blocked UV-induced immune suppression. Moreover, monoclonal anti-CD86 blocked the induction of suppressor T cells normally found in the spleens of the UV-irradiated mice. Monoclonal anti-CD86 also reversed the UV-induced impairment of systemic antigen-presenting cell function. IL-10 was detectable in the serum of UV-irradiated mice as compared with normal controls, and injecting UV-irradiated mice with anti-CD86, but not anti-CD80 or control rat IgG, blocked the secretion of IL-10 into the serum. We propose that UV exposure favours costimulation by CD86, which enhances the production of serum IL-10, thus suppressing Th1-cell-mediated immune reactions.
尽管太阳辐射紫外线(UV)波长所包含的几乎所有能量都在表皮和真皮上层被吸收,但紫外线照射可抑制对在身体远处未受照射部位引入的抗原的免疫反应。紫外线照射的角质形成细胞产生免疫调节细胞因子,如白细胞介素10(IL-10),及其对1型辅助性T细胞(Th1)/Th2细胞平衡的影响,被认为在全身免疫抑制的诱导中起主要作用。因为有研究表明,共刺激分子,如CD80和CD86,对Th1和Th2细胞有不同的刺激作用,所以我们希望研究这些共刺激分子在免疫抑制激活中的作用。我们给紫外线照射的小鼠注射抗CD80和抗CD86单克隆抗体,然后观察这是否会对紫外线诱导的免疫抑制产生影响。抗CD86单克隆抗体,但不是抗CD80单克隆抗体或对照大鼠IgG,可阻断紫外线诱导的免疫抑制。此外,抗CD86单克隆抗体可阻断通常在紫外线照射小鼠脾脏中发现的抑制性T细胞的诱导。抗CD86单克隆抗体还可逆转紫外线诱导的全身抗原呈递细胞功能损伤。与正常对照组相比,在紫外线照射小鼠的血清中可检测到IL-10,给紫外线照射小鼠注射抗CD86单克隆抗体,但不是抗CD80单克隆抗体或对照大鼠IgG,可阻断IL-10分泌到血清中。我们提出,紫外线暴露有利于CD86介导的共刺激,这会增强血清IL-10的产生,从而抑制Th1细胞介导的免疫反应。