Dudda Jan C, Denfeld Ralf W, Simon Jan C, Martin Stefan F
Clinical Research Group Allergology, Department of Dermatology, University of Freiburg, Freiburg, Germany.
J Invest Dermatol. 2004 Apr;122(4):945-52. doi: 10.1111/j.0022-202X.2004.22423.x.
UVB radiation has been shown to induce T cell tolerance most likely via modulation of the function of antigen-presenting cells like dendritic cells (DC), which are therefore of interest for vaccination therapy. Since little is known about the effects of UVB-irradiated dendritic cells (UVB-DC) on CD8(+) T cells, which are the dominant effectors in various allergic and autoimmune diseases, we have investigated the potential of low dose UVB (100-200 J per m(2)) irradiated bone marrow-derived dendritic cells to induce tolerance in murine CD8(+) T cells specific for the contact allergen trinitrophenyl (TNP) or for a viral peptide. In contrast to the previously reported successful tolerization of primed CD4(+) Th1 cells, neither naïve CD8(+) T cells nor CD8(+) Tc1 effector cells or established CD8(+) T cell clones could be tolerized by TNP-modified or peptide-pulsed UVB-DC in vitro or in vivo. We observed, however, a reduced capacity of UVB-DC to prime naïve CD8(+) T cells. Our data demonstrate an important difference in the susceptibility of CD4(+) and CD8(+) T cells for tolerance induction using low-dose UVB-irradiated DC and have implications for DC therapy of CD8(+) T cell-mediated diseases.
已有研究表明,紫外线B(UVB)辐射最有可能通过调节抗原呈递细胞(如树突状细胞,DC)的功能来诱导T细胞耐受,因此DC在疫苗治疗中备受关注。由于人们对UVB照射的树突状细胞(UVB-DC)对CD8(+) T细胞的影响了解甚少,而CD8(+) T细胞是各种过敏性和自身免疫性疾病中的主要效应细胞,我们研究了低剂量UVB(每平方米100 - 200焦耳)照射的骨髓来源树突状细胞诱导对接触性变应原三硝基苯(TNP)或病毒肽特异性的小鼠CD8(+) T细胞耐受的潜力。与先前报道的成功诱导初免CD4(+) Th1细胞耐受不同,无论是未致敏的CD8(+) T细胞、CD8(+) Tc1效应细胞还是已建立的CD8(+) T细胞克隆,在体外或体内都不能被TNP修饰或肽脉冲的UVB-DC诱导耐受。然而,我们观察到UVB-DC激活未致敏CD8(+) T细胞的能力有所降低。我们的数据表明,在使用低剂量UVB照射的DC诱导耐受方面,CD4(+)和CD8(+) T细胞的易感性存在重要差异,这对CD8(+) T细胞介导疾病的DC治疗具有重要意义。