21 May 2009
Rapamycin, unlike cyclosporine a, enhances suppressive functions of in vitro induced CD4+CD25+ TREGS
K Bocian, J Borysowski, P Wierzbicki, J Wyzgał, D Kłosowska, A Białoszewska, L Pączek, A Górski, G Korczak-KowalskaAnn Transplant 2009; 14(1): 36-37 :: ID: 880330
Abstract
Background: A growing amount of data shows that CD4+CD25+ regulatory T
cells (Tregs) can induce transplantation tolerance by suppressing immune responses to allograft antigens. However, both the generation and the suppressive capacity of CD4+CD25+ Tregs can be substantially affected by different immunosuppressive drugs used in clinical transplantation. The goal of this study was to compare the effects of cyclosporine A and rapamycin on the induction and suppressive function of human CD4+CD25+Tregs in vitro.
Material/Methods: CD4+CD25+Tregs were induced in MLR in the presence of rapamycin (Treg-Rapa) or cyclosporine A (Treg-CsA). Tregs were identified by flow cytometry using anti-CD4, anti-CD25, anti-CTLA-4, anti-CD122, anti-GITR, anti-FOXP3 mAbs. Suppressive capacity of induced Tregs was evaluated by their capability to inhibit anti-CD3 Ab-triggered proliferation of PBMCs, as measured by flow cytometry. The concentration of TGF-a1 in culture supernatants was measured by ELISA.
Results: Although both rapamycin and cyclosporine A suppressed the induction of CD4+CD25+Tregs during MLRs, this effect was significantly more pronounced in cells cultured with cyclosporine. On the other hand, only rapamycin significantly decreased the percentage of CD4+CD25+Tregs which expressed GITR, a negative regulator of Treg's suppressive capacity. Importantly, Treg-Rapa, unlike Treg-CsA, displayed significant supressive activity and were capable of inhibiting the proliferation of CD4+ T cells. This activity was likely mediated by TGF-α[sub]1[/sub].
Conclusions: Rapamycin, unlike cyclosporine A, doesn't inhibit the generation of functional CD4+CD25+Tregs. This implies that rapamycin could contribute to the development of transplantation tolerance by promoting the induction of functional CD4+CD25+Tregs. Moreover, our results suggest beneficial effects of combining rapamycin with Tregs.
Keywords: Immunosuppression
In Press
15 Mar 2024 : Review article
Approaches and Challenges in the Current Management of Cytomegalovirus in Transplant Recipients: Highlighti...Ann Transplant In Press; DOI: 10.12659/AOT.941185
18 Mar 2024 : Original article
Does Antibiotic Use Increase the Risk of Post-Transplantation Diabetes Mellitus? A Retrospective Study of R...Ann Transplant In Press; DOI: 10.12659/AOT.943282
20 Mar 2024 : Original article
Transplant Nephrectomy: A Comparative Study of Timing and Techniques in a Single InstitutionAnn Transplant In Press; DOI: 10.12659/AOT.942252
28 Mar 2024 : Original article
Association Between FEV₁ Decline Rate and Mortality in Long-Term Follow-Up of a 21-Patient Pilot Clinical T...Ann Transplant In Press; DOI: 10.12659/AOT.942823
Most Viewed Current Articles
05 Apr 2022 : Original article
Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver TransplantationDOI :10.12659/AOT.935604
Ann Transplant 2022; 27:e935604
12 Jan 2022 : Original article
Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...DOI :10.12659/AOT.934738
Ann Transplant 2022; 27:e934738
22 Nov 2022 : Original article
Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipient...DOI :10.12659/AOT.937988
Ann Transplant 2022; 27:e937988
15 Mar 2022 : Case report
Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...DOI :10.12659/AOT.935860
Ann Transplant 2022; 27:e935860