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

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⁺ T_CM) were increased above the pretransplant level. In 16 type II recipients, IL‐12Rβ1⁺ T_CM was decreased markedly below the pretransplant level on postoperative day (POD) 5. In 17 type III recipients, IL‐12Rβ1⁺ T_CM was decreased for a more prolonged period until POD 10. Along with down‐regulation of IL‐12Rβ1⁺ T_CM, 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⁺ T_CM 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⁺ T_CM 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 T_CM and CNS are regulated in a tightly coupled manner and that expression levels of IL‐12Rβ1⁺ T_CM play a crucial role in controlling allo‐ and infectious immunity.