title: 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.
abstract: Our previous work revealed that the recipients with the highest pre-existing numbers of CD8(+) effector T cells (TE ) [hyperparathyroidism (HPT)E recipients] occupied approximately 30% of adult transplant recipients performed in our hospital. HPTE recipients demonstrated very poor clinical outcome compared with the remaining 70% of recipients with the lowest pre-existing TE (LPTE recipient). This study aimed to clarify the best combined immunosuppressive regimen related to function of cytotoxic T lymphocytes (CTLs) for HPTE recipients. Eighty-one HPTE 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 TE perforin and interferon (IFN)-γ were generated through the self-renewal of CD8(+) central memory T cells (TCM ), but decreased in the early post-transplant period due to marked down-regulation of interleukin (IL)-12 receptor beta-1 of TCM. In type 2, the self-renewal TCM 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(+) TCM levels, and increased at the highest level around the pre-transplant levels of IL-12Rβ1(+) TCM . However, the immunological advantage of Tac/MMF therapy was inhibited strongly by additive steroid administration.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Hepatic Disease Research Institute, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ozawa
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kaido
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mori
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimoto
mesh_terms: D000368:Aged; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D006961:Hyperparathyroidism / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000601:surgery; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D054353:Perforin / Q000235:genetics / Q000276:immunology; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000276:immunology; D012189:Retrospective Studies; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016559:Tacrolimus / Q000627:therapeutic use*; D061349:Unrelated Donors
chemical_list: D007166:Immunosuppressive Agents; C510468:PRF1 protein, human; D053707:Receptors, Interleukin-12; D054353:Perforin; D007371:Interferon-gamma; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008775:Methylprednisolone
keywords: IL-12Rβ1+ cells; central memory T cells; highest pre-existing effector T cells; immunosuppressive regimen; living donor liver transplantation