title: Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents.
abstract: We compared peripheral blood immunophenotyping in 31 adult liver transplant recipients on differing long-term immunosuppressive (IS) monotherapy with and without peri-transplantation alemtuzumab (AL) induction. All patients had been stable on monotherapy with either sirolimus (SRL) (n = 10) or without SRL (tacrolimus (TAC) (n = 10), mycophenolate mofetil (MMF) (n = 11)) for more than 6 months. Five-color flow cytometry for putative "regulatory" T and dendritic cells as well as serum assays for soluble HLA-G (sHLA-G) were performed. The SRL monotherapy group had significantly higher percentages of CD4+CD25(high+)Foxp3+ T cells (1.3 +/- 1.0) compared with the non-SRL group (0.7 +/- 0.6) (p = 0.04). The SRL effect was even higher in a subset with prior AL induction and no prior hepatitis C or rejection (1.7 +/- 0.2) compared with all other subgroups (0.7 +/- 0.6) (p = 0.02). TAC patients showed significantly higher "regulatory" DC2:DC1 ratios (10 +/- 7.6) compared with non-TAC patients (4.1 +/- 2.3) (p = 0.04). Although sHLA-G levels appeared higher in TAC patients, the differences were not statistically significant. In conclusion, IS monotherapy provides an opportunity to investigate regulatory roles of individual agents. SRL maintenance and prior AL induction in subsets of patients appeared to show a regulatory T cell immunophenotype. However, TAC patients may have other regulatory characteristics, supporting the need for larger, prospective studies to clarify differences.
authors.affiliation: Division of Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. j-levitsky@northwestern.edu
authors.forename: Josh
authors.initials: J
authors.lastname: Levitsky
authors.forename: Joshua
authors.initials: J
authors.lastname: Miller
authors.forename: Edward
authors.initials: E
authors.lastname: Wang
authors.forename: Anne
authors.initials: A
authors.lastname: Rosen
authors.forename: Cathy
authors.initials: C
authors.lastname: Flaa
authors.forename: Michael
authors.initials: M
authors.lastname: Abecassis
authors.forename: James
authors.initials: J
authors.lastname: Mathew
authors.forename: Anat
authors.initials: A
authors.lastname: Tambur
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D020123:Sirolimus / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016559:Tacrolimus / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus