Association of CD8+ natural killer T cells in the liver with neonatal tolerance phenomenon

Background. Neonatal tolerance is a very interesting phenomenon, because even allogeneic skin grafts are not rejected in these mice at the adult stage. However, the underlying mechanism remains unclear. Methods. In this study we prepared such tolerant C57BL/6 (B6) mice (H-2(b)) by the injection of allogeneic lymphocytes of BALB/c origin (H-2(d)) at the neonatal stage. Results. The total number of liver lymphocytes in these tolerant mice was found to increase when it was examined at the adult stage. Nevertheless, the retention of allogeneic lymphocytes that were injected at the neonatal stage was highest in the spleen. It is speculated that these allogeneic lymphocytes stimulate the hepatic immune system via the portal vein and that such stimulation maintains the tolerance phenomenon. Indeed, these tolerant mice showed elevated levels of IL-2Rbeta(+) CD3(int) cells (i.e., extrathymic T cells) and NK1.1(+) CD3(int) cells (i.e., NKT cells) in the liver. Even more interestingly, the number and proportion of CD8(+) NKT cells, which are usually a minor population in normal mice, increased among NKT cells in the liver of tolerant mice. This became much more prominent when tolerant mice were grafted with allogeneic (H-2(d)) skin. Conclusion. In conjunction with additional data from a cell-transfer experiment and a splenectomy experiment, our results suggest that CD8(+) NKT cells in the liver of tolerant mice might be intimately associated with the neonatal tolerance phenomenon.