Characteristics of changes in double positive CD4⁺CD8⁺ T cells in liver transplantation

Although double positive CD4⁺CD8⁺ T (DPT) cells has been reported to be involved in some diseases, their trajectory and function as associated with liver transplantation (LT) remain unclear. In the present study, we found that the number of DPT cells was increased in the blood and liver tissue of LT patients. Meanwhile, we compared the distribution of DPT cells in peripheral blood samples and in penetrating liver tissue between liver rejection versus non-rejection patients, as well as the proportion of DPT cells as a function of the extent of liver rejection. The number of DPT cells in the rejection group was significantly increased. An analysis of the spatial distance and correlations between DPT and Treg cells, revealed that these cells showed a high degree of contiguity. In a mouse liver transplant model, the number of DPT cells were significantly increased in liver tissue, and the number of CD8⁺ T cells gradually increased, while CD4⁺ T cells decreased as a function of time post-transplantation. Expression level of PD-1 in DPT cells also increased in a temporally-dependent manner post liver transplantation and the changes of PD-1⁺ DPT cells were related to the degree of liver transplant rejection. In DPT cells interacting with Treg, there was an increased expression of PD-1, which enhanced cellular exhaustion. In conclusion, the capacity for DPT cells to induce immune tolerance may represent a new and important protocol for use in targeting treatments for the prevention of liver transplant rejection.