Saeideh Jamali1, Abdolfatah Sarafnejad1, Pedram Ahmadpoor2, Mohsen Nafar2, Mozhdeh Karimi3, Atefeh Eteghadi3, Mir Saeed Yekaninejad4, Ali Akbar Amirzargar5. 1. Department of Pathobiology, School of Public Healths, Tehran University of Medical Sciences, Tehran, Iran. 2. Chronic Kidney Disease Research Center, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: amirzara@tums.ac.ir.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Abbas Shahi; Saeedeh Salehi; Shima Afzali; Ladan Gol Mohammad Pour Afrakoti; Marzie Esmaeili; Farzaneh Bagherpour; Ziba Aghsaeifard; Sanaz Dehghani; Gholamreza Pourmand; Ali Akbar Amirzargar Journal: Biomed Res Int Date: 2021-02-09 Impact factor: 3.411