Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy

Frontiers in Immunology

Sandra Guiral-Foz¹  David Sansegundo-Arribas¹  Marcos López-Hoyos¹  Rosalia Valero²  Emilio Rodrigo²  Juan Carlos Ruiz²  Jordi Ochando⁴  Paloma Riquelme⁵  James A. Hutchinson⁵  Carmen Pérez⁶  María Iglesias-Escudero⁶  David Merino-Fernández⁶  Patricia Lamadrid-Perojo⁶ 

[1] Department of Immunology, University Hospital Marqués de Valdecilla, Santander, Spain;Department of Nephrology, University Hospital Marqués de Valdecilla, Santander, Spain;Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States;Immunología de Trasplantes, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain;Section of Experimental Surgery, Department of Surgery, University Hospital of Regensburg, Regensburg, Germany;Transplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, Spain;

关键词: kidney transplantation;    mTOR inhibition;    myeloid-derived suppressor cells;    tacrolimus;    immunosuppression;   

DOI  :  10.3389/fimmu.2020.00643

来源: DOAJ

【 摘 要 】

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of myeloid regulatory cells that were originally described in cancer. Several studies in animal models point to MDSC as important players in the induction of allograft tolerance due to their immune modulatory function. Most of the published studies have been performed in animal models, and the data addressing MDSCs in human organ transplantation are scarce. We evaluated the phenotype and function of different MDSCs subsets in 38 kidney transplant recipients (KTRs) at different time points. Our data indicate that monocytic MDSCs (Mo-MDSC) increase in KTR at 6 and 12 months posttransplantation. On the contrary, the percentages of polymorphonuclear MDSC (PMN-MDSC) and early-stage MDSC (e-MDSC) are not significantly increased. We evaluated the immunosuppressive activity of Mo-MDSC in KTR and confirmed their ability to increase regulatory T cells (Treg) in vitro. Interestingly, when we compared the ability of Mo-MDSC to suppress T cell proliferation, we observed that tacrolimus, but not rapamycin-treated KTR, was able to inhibit CD4+ T cell proliferation in vitro. This indicates that, although mTOR inhibitors are widely regarded as supportive of regulatory responses, rapamycin may impair Mo-MDSC function, and suggests that the choice of immunosuppressive therapy may determine the tolerogenic pathway and participating immune cells that promote organ transplant acceptance in KTR.

【 授权许可】

Unknown