Coupled regulation of interleukin-12 receptor beta-1 of CD8+ central memory and CCR7-negative memory T cells in an early alloimmunity in liver transplant recipients


K. Ozawa, Hepatic Disease Research Institute, Honmachi-15chyome-754-1, Higashiyama-ku, Kyoto 605-0981, Japan.


This study investigated how CD8+ T cell subsets respond to allo- and infectious immunity after living donor liver transplantation (LDLT). Early alloimmunity: 56 recipients were classified into three types according to the post-transplant course; type I demonstrated uneventful post-transplant course, type II developed severe sepsis leading to multiple organ dysfunction syndrome or retransplantation and type III with acute rejection. In 23 type I recipients, the interleukin (IL)-12 receptor beta-1 (Rβ1)+ cells of central memory T cells (Il-12Rβ1+ TCM) were increased above the pretransplant level. In 16 type II recipients, IL-12Rβ1+ TCM was decreased markedly below the pretransplant level on postoperative day (POD) 5. In 17 type III recipients, IL-12Rβ1+ TCM was decreased for a more prolonged period until POD 10. Along with down-regulation of IL-12Rβ1+ TCM, the IL-12Rβ1+ cells of CCR7-negative subsets (CNS) as well as perforin, interferon (IFN)-γ and tumour necrosis factor (TNF)-α decreased gradually, resulting in the down-regulation of effectors and cytotoxicity. The down-regulation of IL-12Rβ1+ TCM was suggested to be due to the recruitment of alloantigen-primed T cells into the graft, and then their entry into the secondary lymphoid organ, resulting in graft destruction. Infectious immunity: immunocompetent memory T cells with the capacity to enhance effectors and cytotoxicity were generated in response to post-transplant infection along with both up-regulation of the IL-12Rβ1+ TCM and an increase in the CNS showing the highest level of IL-12Rβ1+ cells. In conclusion, this work demonstrated that the IL-12Rβ1+ cells of TCM and CNS are regulated in a tightly coupled manner and that expression levels of IL-12Rβ1+ TCM play a crucial role in controlling allo- and infectious immunity.