[1677] Effect of Sirolimus and Cyclosporine on Regulatory T Cells in Renal Transplant Allograft

Wei Li, Ping L Zhang. William Beaumont Hospital, Roy Oak, MI

Background: Regulatory T cells (Tregs) have been shown to prevent rejection and lead to improved long-term outcomes. Sirolimus and cyclosporine are wildly used to treat graft rejection, and are known to modulate lymphocyte cellular division and proliferation. The role and effect of these drugs on Tregs in allograft kidney are unclear.
Design: Formalin-fixed paraffin-embedded tissue sections of 66 renal allograft biopsies were immunostained for three markers of Tregs (Foxp3, CD4, and CD8). The number of positive cells in interstitium and tubules was quantified and the data were expressed as the number of cells/mm². The results were compared with biopsies from 16 cases treated with Sirolimus only (Siro), 32 with Sirolimus and Cyclosporine (Siro+Cyclo) and 18 with Cyclosporine only(Cyclo). Clinically relevant levels of proteinuria at the time of biopsy were analyzed in all cases.
Results: The numbers of Foxp3+, CD4+ and CD8+ T cells in interstitium and tubules of renal allograft were significantly greater in Siro group than those in Siro+Cyclo group and Cyclo group. (P<.05 and P<.01, respectively). No significant difference of expression of these regulatory T cells was observed between Siro+Cyclo group and Cyclo group [Table 1]. Proteinuria was significantly higher in Siro (2.98 ± 0.51 g/day) and Siro+Cyclo (2.25 ± 0.41 g/day) groups than Cyclo group (0.71 ± 0.12 g/day (p<0.05).

Table1: Numbers of Foxp3+, CD4+ and CD8+ T cells in interstitium and tubules of renal allograft

Treatment Group (cases)	Foxp3+	CD4+	CD8+
Siro only (16)	9.4 ± 2.4	135 ± 42	261 ± 75
Siro+Cyclo (32)	4.6 ± 1.7	87 ± 27	135 ± 54
Cyclo only (18)	3.1 ± 1.2	79 ± 24	129 ± 39

The number of positive cells in interstitium and tubules was quantified and the data were expressed as the number of cells/mm2


Conclusions: Sirolimus appears to increase the number of Tregs whereas cyclosporine decreases the number of Tregs in allograft kidney, suggesting that immunosuppressive drugs have differential effects on Tregs. Examination of expression of Tregs may have the potential to inform immunosuppressive regimen manipulation to improve outcomes of allograft. Our results also confirm previous reports of a significant increase of proteinuria in kidney transplant recipients treated with Sirolimus.
Category: Kidney (does not include tumors)

Wednesday, March 21, 2012 1:00 PM

Poster Session VI # 302, Wednesday Afternoon