Advantage of tacrolimus/mycophenolate mofetil regimen for cytotoxic T cell‐mediated defence and its inhibition by additive steroid administration in high‐risk liver transplant recipients

Summary Our previous work revealed that the recipients with the highest pre‐existing numbers of CD8 + effector T cells (T E ) [hyperparathyroidism (HPT) E recipients] occupied approximately 30% of adult transplant recipients performed in our hospital. HPT E recipients demonstrated very poor clinical outcome compared with the remaining 70% of recipients with the lowest pre‐existing T E (LPT E recipient). This study aimed to clarify the best combined immunosuppressive regimen related to function of cytotoxic T lymphocytes (CTLs) for HPT E recipients. Eighty‐one HPT E recipients were classified into three types, according to the immunosuppressive regimens: type 1, tacrolimus (Tac)/glucocorticoid (GC); type 2, Tac/mycophenolate mofetil (MMF)/GC; and type 3, Tac/MMF. Frequencies of severe infection, rejection and hospital death were the highest in types 1 and 2, whereas the lowest occurred in type 3. The survival rate in type 3 was the highest (100%) during follow‐up until post‐operative day 2000. Regarding the immunological mechanism, in type 1 T E perforin and interferon (IFN)‐γ were generated through the self‐renewal of CD8 + central memory T cells (T CM ), but decreased in the early post‐transplant period due to marked down‐regulation of interleukin (IL)‐12 receptor beta‐1 of T CM. In type 2, the self‐renewal T CM did not develop, and the effector function could not be increased. In type 3, in contrast, the effectors and cytotoxicity were correlated inversely with IL‐12Rβ1 + T CM levels, and increased at the highest level around the pre‐transplant levels of IL‐12Rβ1 + T CM . However, the immunological advantage of Tac/MMF therapy was inhibited strongly by additive steroid administration.