Wu M F, Raulet D H
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
J Immunol. 1997 Feb 15;158(4):1628-33.
NK cells in normal mice reject bone marrow transplants from class I-deficient mice. In contrast, class I-deficient mice do not reject autologous cells, suggesting that NK cell tolerance is acquired. We employed fetal liver irradiation chimeras to assess two potential mechanisms that could account for the tolerance of NK cells in class I-deficient mice to class I-deficient cells: 1) a positive model, in which recognition of class I+ cells molecules by NK cells is necessary to induce functional NK cell maturation; and 2) a negative model, in which interactions of NK cells with class I-deficient cells induce tolerance. In class I+ chimeras reconstituted with mixtures of class I+ and class I-deficient fetal liver cells, the rejection of class I-deficient bone marrow cell grafts was significantly impaired, supporting the negative model. We further addressed whether nonhemopoietic cells are also able to induce NK cell tolerance. Class I- mice reconstituted with class I+ fetal liver cells were tolerant of class I-deficient cells, favoring this idea. Furthermore, class I-deficient mice reconstituted with a mixture of class I-deficient and class I+ fetal liver cells were more tolerant to class I-deficient cells than were class I+ mice reconstituted with the same fetal liver cell mixture. These results suggest that maximal tolerance induction requires the presence of class I-deficient nonhemopoietic cells.
正常小鼠中的自然杀伤细胞（NK细胞）会排斥来自I类分子缺陷小鼠的骨髓移植。相比之下，I类分子缺陷小鼠不会排斥自体细胞，这表明NK细胞的耐受性是后天获得的。我们利用胎肝照射嵌合体来评估两种可能解释I类分子缺陷小鼠中NK细胞对I类分子缺陷细胞产生耐受性的潜在机制：1）阳性模型，即NK细胞识别I类分子阳性细胞分子对于诱导功能性NK细胞成熟是必要的；2）阴性模型，即NK细胞与I类分子缺陷细胞的相互作用诱导耐受性。在用I类分子阳性和I类分子缺陷胎肝细胞混合物重建的I类分子阳性嵌合体中，I类分子缺陷骨髓细胞移植的排斥反应明显受损，这支持了阴性模型。我们进一步探讨了非造血细胞是否也能够诱导NK细胞耐受性。用I类分子阳性胎肝细胞重建的I类分子阴性小鼠对I类分子缺陷细胞具有耐受性，这支持了这一观点。此外，用I类分子缺陷和I类分子阳性胎肝细胞混合物重建的I类分子缺陷小鼠比用相同胎肝细胞混合物重建的I类分子阳性小鼠对I类分子缺陷细胞更具耐受性。这些结果表明，最大程度的耐受性诱导需要存在I类分子缺陷的非造血细胞。
