Different immunosuppressive combinations on T-cell regulation in renal transplant recipients.

Recent studies indicate that regulatory T-cells (Tregs) promote transplant tolerance. We studied Treg levels in 39 stable renal transplant recipients to determine the sizes of the Treg populations and the effects of treatment regimens thereof. All patients (19 with good graft function and 20 with chronic allograft nephropathy) received induction therapy (basiliximab) and were on triple immunosuppressive regimens with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil (MMF) or everolimus and steroids. Twenty healthy subjects served as controls. Whole blood samples were stained with anti-CD4, CD25, CD127, and FoxP3 antibodies and analyzed by flow cytometry to determine CD4+CD25(high)FoxP3+/- and CD4+ CD25(high)CD127(-/low) Treg levels. All patients had significantly reduced CD4+CD25(high)FoxP3+/- but no CD4+ CD25(high)CD127(-/low) Treg levels compared to controls. Renal allograft function did not correlate with Treg levels. Statistically significant correlations between CD4+CD25(high)Foxp3+ Tregs and tacrolimus levels and CD4+CD25(high)Foxp3- Tregs and HLA-DR mismatching were detected. Patients receiving MMF had significantly higher CD4+CD25(high)Foxp3+ Tregs compared to patients on everolimus who were also receiving lower doses of calcineurin inhibitors. Overall, immunosuppression lowers CD4+CD25(high)FoxP3+/- Treg levels significantly in the periphery in renal transplant recipients. In addition, different immunosuppressive regimens have different impacts on CD4+CD25(high)FoxP3+ Tregs, a fact that may influence long-term allograft survival.

Fourtounas C ，Dousdampanis P ，Sakellaraki P ，Rodi M ，Georgakopoulos T ，Vlachojannis JG ，Mouzaki A ... -  《-》

Sirolimus vs mycophenolate moftile in Tacrolimus based therapy following induction with Antithymocyte globulin promotes regulatory T cell expansion and inhibits RORγt and T-bet expression in kidney transplantation.

Accumulating evidence suggests that regulatory T cells (Tregs) have a crucial role in immune tolerance and long-term graft survival. However, the influence of immunosuppressive drugs on the level of Tregs has not been fully understood. Therefore we prospectively compare the effect of two different calcineurin inhibitor (CNI)-based immunosuppression protocols on Tregs frequencies and expression of regulatory and effector T cell-related genes in renal transplant recipients. The study included 24 renal transplant recipients who received induction therapy (Antithymocyte globulin) and were on triple immunosuppressive therapy so that one group was on Tacrolimus (Tac), mycophenolate moftile (MMF) and prednisolone (P) whereas another group was on Tac, Sirolimus (SRL) and P. The frequency of circulating Treg cells was analyzed by flow cytometry before and 4 months after transplantation. Also, the mRNA expression of FOXP3, T-bet, GATA3 and RORγt was examined by quantitative RT-PCR before and 4 months after transplantation. Compared to baseline, the frequency of CD4+ CD25+ FOXP3+ Treg cells was significantly increased in the all patients following transplantation. Patients who received Tac/MMF had significantly higher CD4+ CD25+ FOXP3+ Treg cells compared to patients who received Tac/SRL. There was no a significant difference in the frequency of CD3+CD8+ CD28- Tregs between two different calcineurin inhibitor (CNI)-based immunosuppression protocols. FOXP3 mRNA levels in the patients who received Tac/MMF were increased 4 months after transplantation and the expression was significantly higher than patients who received Tac/SRL. On the other hand, T-bet and RORγt expression levels were significantly lower in the Tac/SRL group in comparison to Tac/MMF group. We did not observe any significant difference in GATA3 mRNA level between the two groups. Our results suggest that although Tac/MMF-containing immunosuppressive regimen could significantly increase the frequency of CD4+ CD25+ FOXP3+ Tregs, unlike to Tac/SRL-containing regimen, it could not significantly decrease the expression levels of RORγt and T-bet.

Jamali S ，Sarafnejad A ，Ahmadpoor P ，Nafar M ，Karimi M ，Eteghadi A ，Yekaninejad MS ，Amirzargar AA ... -  《-》

[Regulatory T cells in kidney transplant recipients].

Libetta C ，Portalupi V ，Margiotta E ，Sepe V ，Canevari M ，Meloni F ，Morosini M ，Dal Canton A ... -  《-》

Clinical rejection and persistent immune regulation in kidney transplant patients.

Hendrikx TK ，Klepper M ，Ijzermans J ，Weimar W ，Baan CC ... -  《-》

Comparison of four different immunosuppression protocols without long-term steroid therapy in kidney recipients monitored by surveillance biopsy: five-year outcomes.

Anil Kumar MS ，Irfan Saeed M ，Ranganna K ，Malat G ，Sustento-Reodica N ，Kumar AM ，Meyers WC ... -  《TRANSPLANT IMMUNOLOGY》