Abbas Shahi1,2, Saeedeh Salehi1, Shima Afzali1, Ladan Gol Mohammad Pour Afrakoti1, Marzie Esmaeili1, Farzaneh Bagherpour3, Ziba Aghsaeifard4, Sanaz Dehghani3, Gholamreza Pourmand5, Ali Akbar Amirzargar1. 1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Student's Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Organ Procurement Unit, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Internal Medicine, School of Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Urology, School of Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: Regulatory T cells (Tregs) and recent thymic emigrants (RTEs) have an essential role in the regulation of allogeneic immune responses. However, their mechanisms of action in chronic antibody-mediated rejection (cAMR) are still unclear. In this study, we aimed to compare Treg and RTE levels between stable graft function (SGF) patients and cAMR subjects after kidney transplantation. METHOD: Mononuclear cells (MNs) were separated from peripheral blood, and flow cytometry analysis was performed for detection of CD4+ and CD25high as Treg markers and CD4+, CD31+, and CD45RA+ as RTE immunophenotyping markers. RESULT: The level of peripheral Treg cells was significantly lower in cAMR subjects in comparison to stable graft function patients. Moreover, SGF patients who had received cyclosporine A had a higher level of Treg in comparison to the tacrolimus recipients. Nevertheless, the RTE level between SGF and cAMR patients did not show any significant differences. CONCLUSION: It seems that Treg cells are significantly associated with transplant outcomes in cAMR patients, and prescribed immunosuppressive drugs can influence the frequency of this crucial subset of T cells. Although these drugs are beneficial and inevitable for allograft maintenance, more investigations are needed to elucidate their complete effects on different immune cell subsets which some of them like Tregs are in favor of transplant tolerance. Besides, the thymic output is seemingly not a beneficial biomarker for predicting cAMR; however, more in vivo and in vitro studies are needed for revealing the precise role of Tregs and RTEs in the transplantation context.
BACKGROUND: Regulatory T cells (Tregs) and recent thymic emigrants (RTEs) have an essential role in the regulation of allogeneic immune responses. However, their mechanisms of action in chronic antibody-mediated rejection (cAMR) are still unclear. In this study, we aimed to compare Treg and RTE levels between stable graft function (SGF) patients and cAMR subjects after kidney transplantation. METHOD: Mononuclear cells (MNs) were separated from peripheral blood, and flow cytometry analysis was performed for detection of CD4+ and CD25high as Treg markers and CD4+, CD31+, and CD45RA+ as RTE immunophenotyping markers. RESULT: The level of peripheral Treg cells was significantly lower in cAMR subjects in comparison to stable graft function patients. Moreover, SGF patients who had received cyclosporine A had a higher level of Treg in comparison to the tacrolimus recipients. Nevertheless, the RTE level between SGF and cAMR patients did not show any significant differences. CONCLUSION: It seems that Treg cells are significantly associated with transplant outcomes in cAMR patients, and prescribed immunosuppressive drugs can influence the frequency of this crucial subset of T cells. Although these drugs are beneficial and inevitable for allograft maintenance, more investigations are needed to elucidate their complete effects on different immune cell subsets which some of them like Tregs are in favor of transplant tolerance. Besides, the thymic output is seemingly not a beneficial biomarker for predicting cAMR; however, more in vivo and in vitro studies are needed for revealing the precise role of Tregs and RTEs in the transplantation context.
Authors: A Sannier; N Stroumza; G Caligiuri; M Le Borgne-Moynier; F Andreata; J Senemaud; L Louedec; G Even; A T Gaston; C Deschildre; A Couvelard; P Ou; R Cheynier; P Nataf; R Dorent; A Nicoletti Journal: Am J Transplant Date: 2017-12-23 Impact factor: 8.086
Authors: A Hart; J M Smith; M A Skeans; S K Gustafson; A R Wilk; S Castro; A Robinson; J L Wainright; J J Snyder; B L Kasiske; A K Israni Journal: Am J Transplant Date: 2019-02 Impact factor: 8.086
Authors: Jose R Torrealba; Masaaki Katayama; John H Fechner; Ewa Jankowska-Gan; Satoshi Kusaka; Qingyong Xu; Jacqueline M Schultz; Terry D Oberley; Huaizhong Hu; Majed M Hamawy; Margreet Jonker; Jacqueline Wubben; Gaby Doxiadis; Ronald Bontrop; William J Burlingham; Stuart J Knechtle Journal: J Immunol Date: 2004-05-01 Impact factor: 5.422