The beneficial effect of renal transplantation on the immune phenotype of T lymphocytes
Lampros Vagiotas 11, Asimina Fylaktou 22, Efstratios Kassimatis 33, Aliki Xochelli 22, Erasmia Sampani 33, Vasiliki Nikolaidou 22, Maria Daoudaki 43, George Tsoulfas 11, Aikaterini Papagianni 33, Maria Stangou 33.
1Department of Transplantation Surgery, Hippokration Hospital, Aristotle University School of Medicin, Thessaloniki, Greece; 2Department of Immunology, National Peripheral Histocompatibility Center, Hippokration Hospital, Thessaloniki, Greece; 3Department of Nephrology, Hippokration Hospital, Aristotle University School of Medicin, Thessaloniki, Greece
Introduction: Changes which happen on the phenotype of T lymphocytes during chronic kidney disease CKD, include reduction of CD4CD25FoxP3(Tregs) and increase in CD28null and CD16CD56(NKs) cells. These alterations are expected be restored following kidney transplantation.
Patients-Methods: In this prospective study, we included patients with CKD (Ν=71), who were transplanted and followed for up to 12 months. The same immunosuppressive protocol was used to all patients, including steroids, Calcineurine inhibitors and mycophenolate mofetil, with or without ATG. Cytometric analysis was performed at time point T0 (day of transplantation) and, then at Τ3, Τ6, Τ12 (3,6,12 months after transplantation, respectively), to estimate the phenotype of T lymphocytes. Based on this analysis T lymphocyte subtypes studied were: CD4, CD8, CD4CD28null, CD8CD28null, NKs, Tregs.
Results: A remarkable and sustained increase in the population of total lymphocytes, as well as of CD4 [510(331), 764(606), 857(661), p<0.0001], CD8 [290(188), 434(318), 528(312), p<0.0001], NKs [198(152), 126(134), 142(152), p<0.001) and Tregs [21(18), 24(20), 34(26), p<0.001], was noticed at time points T0-T3-T6, respectively. All subpopulations remained stable thereafter, during the time period T6-T12.
At time point T0, patients who had been on chronic hemodialysis (HD) (N=64) had significantly reduced numbers of Tregs, compared to those undergoing Pre-emptive transplantation (N=7), p=0,006, and increased number of CD8CD28null cells (p=0.006). Furthermore, Treg population had significantly negative correlation with dialysis vintage, r=-0.5, p=0.004.
At time point Τ12, Treg population had significant correlation with previous HD, delayed graft function (DGF) and administration of ATG, (p=0.02, p=0.004, p=0.04, respectively. CD8CD28null cells had significant correlation only with the presence of positive Panel Reactive Antibody, p=0.04.
Conclusions: The beneficial effect of renal transplantation was prompt and evident mainly in the subpopulations of regulatory T cell and NKs, especially in patients undergoing Pre-emptive transplant, however the detrimental effect of HD on CD8 molecule did not seem to be restored during the 12 month period of follow up.
