The role of N K T Cells in Transplantation

该模型中的自然杀伤T细胞显示出诱导加速排斥。这种效应可能是NK细胞特异性的，或者是NK细胞（分泌细胞因子）和T细胞（作为同种细胞毒性效应物）之间合作的结果。从我们的研究来看，不仅T细胞，而且NK细胞可能在器官移植排斥反应中发挥作用。NK-T细胞可诱导器官移植免疫耐受。然而，这一机制利用特异性免疫治疗诱导耐受或增加抗癌细胞毒活性需要进一步研究。这些数据证实了宿主NK细胞在干细胞同种异体移植中的抑制作用。我们已经证明了抗NK治疗的有益效果。用抗去唾液酸-GM 1治疗提供了改善受体免疫调节的手段，并且没有显示出有害作用。NK细胞活性实际上在短暂抑制后几周恢复，这可能对维持稳定的嵌合状态有很大贡献。我们的数据是与致命的照射模型重建更重要的半同种异体FLCT与成熟的T细胞供体，这成为激活和释放细胞因子的混合获得的。CD 3 ^+ /CD 56 ^+细胞在新鲜分离的UCB中含量较低，在批量MLC中显著增殖，并代表了单细胞克隆后的大多数应答者。这些细胞表达CD 8 ^+表型，少数N-特异性细胞增殖并表现出MHC限制性杀伤活性。UCB克隆的细胞因子产量低于PB克隆，尽管它们具有更强的杀伤活性。表达CD 56 ^+标记物的CD 3 ^+ CD 8 ^+ T细胞可能是诱导GVHD的主要细胞。它们应该在HLA不匹配的UCB移植中得到证实。

Natural killer T cells in this model were shown to induce accelerated rejection. This effect could be specific for the NK cells or would be the results of a cooperation between the NK cells (secretion of cytokines) and T cells (as allocytotoxic effectors). From our study, not only T cells but also NK cells may play a role in organ transplantation rejection. NK-T cells may induce immune tolerance in organ transplantation. However, this mechanism using specific immune therapy for the induction of tolerance or to increase anti-cancer cytotoxic activity needs further study. These data confirm the inhibitory role of host NK cells in stem cell allogeneic engraftment. We have demonstrated the beneficial effect of anti-NK treatment. Treatment with anti-asialo-GM1 provides a means for improving the immunologjc conditioning of the recipient and showed no harmful effects. NK-cell activity was actually restored a few week after a brief inhibition, which may contribute strongly to maintaining a stable chimerism. Our data are comparable to those obtained with a lethally irradiated model reconstituted by more important semi-allogeneic FLCT mixed with a mature T-cell donor-which became activated and released cytokines. CD3^+ /CD56^+ cells, low in freshly isolated UCB, proliferated significantly in bulk MLC and represented a majority of the responders after single cell cloning. These cells expressed the CD8^+ phenotype and a few N-specific cells proliferated and exhibited an MHC-restricted killing activity. Cytokine production on the UCB clones was lower than in the PB clones, despite their stronger killing activity. The CD3^+ CD8^+ T cells, expressing, the CD56^+ marker, could be the major cells responsible for title induction of GVHD. They should be proven in HLA-mismatched UCB transplantation.