Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents.
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.
Levitsky
Josh
J
Division of Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. j-levitsky@northwestern.edu
Miller
Joshua
J
Wang
Edward
E
Rosen
Anne
A
Flaa
Cathy
C
Abecassis
Michael
M
Mathew
James
J
Tambur
Anat
A
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
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