FoxP3 in Peripheral Blood Is Associated With Operational Tolerance in Liver Transplant Patients During Immunosuppression Withdrawal

• Published in: Transplantation Vol. 86; no. 10; pp. 1370 - 1378
• Main Authors: STEPKOWSKI, Stanislaw M, PONS, José A, PARRILLA, Pascual, REVILLA-NUIN, Beatriz, BAROJA-MAZO, Alberto, RAMIREZ, Pablo, MARTINEZ-ALARCON, Laura, SANCHEZ-BUENO, Francisco, ROBLES, Ricardo, RIOS, Antonio, APARICIO, Pedro
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 27-11-2008
• Subjects: Antigens, CD - immunology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Cyclosporine - administration & dosage; Cyclosporine - therapeutic use; Drug Administration Schedule; Female; Forkhead Transcription Factors - blood; Forkhead Transcription Factors - genetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Survival - immunology; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - therapeutic use; Interleukin-2 Receptor alpha Subunit - immunology; Liver Cirrhosis, Alcoholic - surgery; Liver Transplantation - immunology; Male; Medical sciences; Middle Aged; Retrospective Studies; RNA, Messenger - genetics; Substance Withdrawal Syndrome - physiopathology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; T-Lymphocytes, Regulatory - immunology; Tissue, organ and graft immunology; Transplantation Tolerance - physiology; Transplantation, Homologous; Human; Digestive system; Liver; Patient; Transplantation; Homotransplantation; Blood; Immunosuppression; Association; Treatment; Surgery; Treatment withdrawal; Immune tolerance; Graft; Transcription factor; Transcription factor FOXP3
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/TP.0b013e318188d3e6

Human liver allografts do sometimes survive in a recipient after withdrawal of immunosuppression (IS), commonly referred to as "operational tolerance." Preliminary clinical data have suggested an increase in the frequency of regulatory T cells (Treg) CD4+CD25 high and FoxP3 expression in operationally tolerant liver transplant recipients (Gr-T). In the context of human liver transplantation, the dynamics of Treg have not been studied. We designed a prospective study to ascertain the profile of the Treg population and FoxP3 expression during IS withdrawal.
To identify such parameters, we analyzed peripheral blood mononuclear cell populations and FoxP3 mRNA expression in 12 liver allograft recipients under cyclosporine A-based IS, who showed stable function of the allograft for more than 2 years.
An increase was observed in the frequency of CD4+CD25 high cells when the IS was withdrawn in Gr-T patients (n=5). These patients exhibited a 3.5-fold increase for relative mRNA FoxP3 expression before the complete IS withdrawal and this continued when IS therapy was stopped. In patients who suffered rejection (n=7) there was no increase in the CD4+CD25 high cells or FoxP3 expression.
With the present study, the first evidence is provided that the increase of CD4+CD25 high T cells and FoxP3 transcripts is associated with operational tolerance in liver transplanted patients during IS withdrawal.