WOFIE stimulates regulatory T cells: a 2-year follow-up of renal transplant recipients.
BACKGROUND
Initial interruption of immunosuppression for 72 hr was analyzed in renal transplant recipients according to Calne et al.'s "window of opportunity for immunologic engagement" (WOFIE) concept.


METHODS
This pilot study was designed as a randomized, open-label, prospective trial of 40 recipients (20 in the WOFIE group, 20 in the control group) of cadaveric kidney transplants who were followed up for 2 years. Immunosuppression comprised tacrolimus (trough levels 5-8 ng/mL), daclizumab (1 mg per kilogram of body weight on day 0 and after 2, 4, 6, and 8 weeks), mycophenolate mofetil (1-2 g/day), and prednisolone (maintenance dose of 10 mg/day). After induction with daclizumab, prednisolone, and mycophenolate mofetil, immunosuppression was interrupted for 72 hr in the WOFIE group. Steroid withdrawal followed in both groups within 12 to 16 weeks posttransplant.


RESULTS
Patient and graft survival did not differ significantly between the two cohorts. However, the WOFIE group experienced less acute rejection episodes and developed better graft function. Although all but one of the patients in the WOFIE group successfully discontinued steroid treatment, permanent steroid withdrawal was achieved in only 76.4% of the control group. After daclizumab discontinuation, the WOFIE group demonstrated an increase of CD4CD25 T cells in peripheral blood (P<0.05 vs. control group), which was stable over time and strongly correlated with a significantly higher expression level of Foxp3-mRNA.


CONCLUSIONS
Initial interruption of immunosuppression for 72 hr correlates with the induction of regulatory immunologic mechanisms and allows early and reliable minimization of immunosuppressive treatment.
Dresske
Bettina
B
Department of General and Thoracic Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany. BDresske@gmx.de
Haendschke
Frank
F
Lenz
Philine
P
Ungefroren
Hendrik
H
Jenisch
Stefan
S
Exner
Beate
B
El Mokhtari
Nour Eddine
NE
Lu
Tim
T
Zavazava
Nicholas
N
Faendrich
Fred
F
D000293:Adolescent; D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014180:Transplantation / Q000502:physiology; D014181:Transplantation Immunology; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology*
D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2