UVB-irradiated dendritic cells fail to tolerize murine CD8+ naive or effector T cells

UVB-irradiated dendritic cells fail to tolerize murine CD8+ naive or effector T cells
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DOI:
10.1111/j.0022-202x.2004.22423.x
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发表时间:
2004-04-01
影响因子:
6.5
通讯作者:
Martin, SF
Martin, SF
中科院分区:
医学1区
文献类型:
--
作者:
Dudda, JC;Denfeld, RW;Martin, SF

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UVB辐射已显示最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细胞耐受性,因此其对于疫苗接种疗法是感兴趣的。由于对UVB照射的树突状细胞(UVB-DC)对CD 8(+)T细胞的影响知之甚少,而CD 8(+)T细胞是各种过敏性和自身免疫性疾病中的主要效应物,我们研究了低剂量UVB(100 - 200 J/m2)照射骨髓来源的树突状细胞诱导小鼠CD 8 + T细胞对接触性过敏原三硝基苯基(TNP)的耐受性或用于病毒肽。与先前报道的致敏的CD 4(+)Th 1细胞的成功耐受相反,无论是初始的CD 8(+)T细胞还是CD 8(+)Tc 1效应细胞或建立的CD 8(+)T细胞克隆都不能被TNP修饰的或肽脉冲的UVB-DC在体外或体内耐受。然而,我们观察到UVB-DC引发初始CD 8(+)T细胞的能力降低。我们的数据表明,在使用低剂量UVB照射的DC诱导耐受时,CD 4(+)和CD 8(+)T细胞的易感性存在重要差异,并对CD 8(+)-T细胞介导的疾病的DC治疗具有意义。
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 (100200 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 naive 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 naive 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.