Roelofs-Haarhuis Karin, Wu Xianzhu, Nowak Michael, Fang Min, Artik Suzan, Gleichmann Ernst
Institut für umweltmedizinische Forschung and Dermatology Clinic, Heinrich Heine University, Düsseldorf, Germany.
J Immunol. 2003 Sep 15;171(6):2863-72. doi: 10.4049/jimmunol.171.6.2863.
Previously, we reported that tolerance to nickel, induced by oral administration of Ni(2+) ions, can be adoptively transferred to naive mice with only 10(2) splenic T cells. Here we show that 10(2) T cell-depleted spleen cells (i.e., APCs) from orally tolerized donors can also transfer nickel tolerance. This cannot be explained by simple passive transfer of the tolerogen. The APCs from orally tolerized donors displayed a reduced allostimulatory capacity, a tolerogenic phenotype, and an increased expression of CD38 on B cells. In fact, it was B cells among the APCs that carried the thrust of tolerogenicity. Through serial adoptive transfers with Ly5.1(+) donors and two successive sets of Ly5.2(+) recipients, we demonstrated that nickel tolerance was infectiously spread from donor to host cells. After the transfer of either T cells or APCs from orally tolerized donors, the spread of tolerance to the opposite cell type of the recipients (i.e., APCs and T cells, respectively) required recipient immunization with NiCl(2)/H(2)O(2). For the spread of tolerance from a given donor cell type, T cell or APC, to the homologous host cell type, the respective opposite cell type in the host was required as intermediate. We conclude that T suppressor cells and tolerogenic APCs induced by oral administration of nickel are part of a positive feedback loop that can enhance and maintain tolerance when activated by Ag associated with a danger signal. Under these conditions, APCs and T suppressor effector cells infectiously spread the tolerance to naive T cells and APCs, respectively.
此前，我们报道口服Ni(2+)离子诱导的镍耐受性可通过仅10(2)个脾T细胞过继转移至未致敏小鼠。在此我们表明，来自经口服耐受供体的10(2)个去除T细胞的脾细胞（即抗原呈递细胞）也能转移镍耐受性。这无法用耐受原的简单被动转移来解释。来自经口服耐受供体的抗原呈递细胞表现出降低的同种异体刺激能力、致耐受性表型以及B细胞上CD38表达增加。事实上，抗原呈递细胞中的B细胞承载着致耐受性的主要作用。通过用Ly5.1(+)供体和两组连续的Ly5.2(+)受体进行系列过继转移，我们证明镍耐受性从供体细胞感染性地传播至宿主细胞。从经口服耐受供体转移T细胞或抗原呈递细胞后，耐受性向受体的相反细胞类型（即分别为抗原呈递细胞和T细胞）的传播需要用NiCl(2)/H(2)O(2)对受体进行免疫。为了使耐受性从给定的供体细胞类型（T细胞或抗原呈递细胞）传播至同源宿主细胞类型，宿主中相应的相反细胞类型作为中间环节是必需的。我们得出结论，口服镍诱导的T抑制细胞和致耐受性抗原呈递细胞是正反馈回路的一部分，当被与危险信号相关的抗原激活时，该回路可增强并维持耐受性。在这些条件下，抗原呈递细胞和T抑制效应细胞分别将耐受性感染性地传播至未致敏T细胞和抗原呈递细胞。
