Dynamics of CD25 Positive Myeloid Derived Suppressor Cells in Solid Organ Transplanted Patients and Relationship with Rejection

Abstract

Backgound Myeloid derived suppressor cells (MDSC) are immature cells with immunosuppressive capacities. Three MDSC subsets are currently defined: monocytic, early stage, and polymorphonuclear MDSC (M-MDSC, eMDSC and PMN-MDSC respectively). While MDSC increase in cancer and chronic infections and associate with poor prognosis, their role in transplantation (Tx) is unknown. Changes in MDSC in transplant patients could provide biomarkers of graft evolution, and they could be useful as immunosuppressive therapy and/or to stimulate the allograft tolerance. Methods Peripheral blood MDSC were identified in cohorts of kidney (n=164) and liver (n=30) recipients and healthy volunteers (HV) as CD33+CD11b+HLA-DRlo/-. We characterized CD14+CD15- (M-MDSC) and CD14-CD15- (eMDSC) subsets. Suppression assays and measurement of surface CD25 expression (MFI) on MDSC were performed. Results Renal recipients MDSC were able to suppress CD4 and CD8 T cell proliferation in vitro. MDSC % were similar in pre-transplant, kidney transplant recipients (KTR), than in HV. However, MDSC and M-MDSC increased, mainly at 7 and 14 days post-transplant (3.48% and 3.85% vs 1.14%; 2.47% and 2.48% vs 0.24% p≤0,001 vs pre-transplant). The increase of MDSC in KTR with basiliximab as induction therapy was lower than in patients induced with thymoglobulin or without induction, and eMDSC were particularly decreased in basiliximab-treated patients (vs no induction, p≤0.05; vs thymoglobulin, p≤0.05). We confirmed that eMDSC expressed CD25, target of basiliximab. Pre-Tx, liver transplant recipients (LTR) had higher % of CD25+ eMDSC and higher CD25 MFI than KTR and HV. In LTR and KTR without basiliximab, % and MFI of CD25 in eMDSC increased after transplant. In KTR cohort, 7% of patients suffered acute rejection (AR). Absolute numbers of MDSC at 7 days post-transplant (measured before the rejection event) were significantly lower in AR than in non-rejectors (25.84 cells/uL vs 53.18 cells/uL respectively, p≤0,05). Conclusions MDSC and M-MDSC increase post-Tx except in patients receiving basiliximab. MDSC were lower in AR patients and low MDSC counts significantly preceded rejection. Transplant recipients eMDSC express CD25 which upregulates after Tx. Whether eMDSC express a complete and functional IL-2R is under investigation.