Myeloid-derived suppressor cells expand after transplantation and their augmentation increases graft survival

Abstract

Myeloid‐derived suppressor cells (MDSCs) expand in an inflammatory microenvironment such as cancer and autoimmunity. To study if transplantation induces MDSCs and these cells regulate allograft survival, C57BL/6 donor hearts were transplanted into BALB/c recipients and endogenous MDSCs were characterized. The effects of adoptive transfer of transplant (tx), tumor (tm), and granulocyte‐colony stimulating factor (g‐csf)–expanded MDSCs or depletion of MDSC were assessed. MDSCs expanded after transplantation (1.7‐4.6‐fold) in the absence of immunosuppression, homed to allografts, and suppressed proliferation of CD4 T cells in vitro. Tx‐MDSCs differed phenotypically from tm‐MDSCs and g‐csf‐MDSCs. Among various surface markers, Rae‐1 expression was notably low and TGF‐β receptor II was high in tx‐MDSCs when compared to tm‐MDSCs and g‐csf‐MDSCs. Adoptive transfer of these three MDSCs led to differential graft survival: control (6 days), tx‐MDSCs (7.5 days), tm‐MDSCs (9.5 days), and g‐csf‐MDSCs (19.5 days). In combination with anti‐CD154 mAb, MDSCs synergistically extended graft survival from 40 days (anti‐CD154 alone) to 86 days with tm‐MDSCs and 132 days with g‐csf‐MDSCs. Early MDSC depletion (day 0 or 20), however, abrogated graft survival, but late depletion (day 25) did not. In conclusion, MDSCs expanded following transplantation, migrated to cardiac allografts, prolonged graft survival, and were synergistic with anti‐CD154 mAb.

Review: Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation

“…Interestingly, myeloid cell secreting S100A9 express the myeloid-derived suppressor cells (MDSC) associated markers CD33, CD163, and DC-SIGN. MDSC have drawn particular interest in the field of transplant immunology, as systemic inflammation mobilizes immature myeloid cells from bone marrow into the circulation and the injured tissue where they may differentiate into MDSCs [104,105]. This is consistent with a recent study that reported the natural expansion of MDSCs following heart allograft transplantation in mice that favor graft survival prolongation [106].…”

Cellular and Antibody Immunity after COVID-19 Vaccination at >4-Month Follow Up in Immunocompetent and Immunocompromised Subjects

“…These associations are supported by studies in which PMN-MDSC inhibit B-cell proliferation and antibody production (Lelis, Knier) (17,18). However, MDSC are also known to expand in IC populations such as transplant recipients, and cancer patients (Lee, Feng, Cassetta) (19)(20)(21). This expansion was not apparent in vaccinated IC subjects with RBD-IgG, in whom M-MDSC and PMN-MDSC frequencies approximated those seen in immunocompetent subjects.…”

Specific Blood Cells Derived from Pluripotent Stem Cells: An Emerging Field with Great Potential in Clinical Cell Therapy

“…It is the result of interaction between donor T cells and recipient antigen-presenting cells (APCs) [ 57 ], which can be a devastating complication for as many as one-third of patients undergoing allo-HSCT [ 58 ]. Due to the unique functional characteristic of suppression to alloreactive T cell responses [ 59 ], MDSCs have stirred up interest among transplant immunologists in their potential clinical merits. Expectedly, researchers have demonstrated that GVHD can be efficiently prevented by MDSCs without influencing graft-versus-leukemia (GVL) effect in murine models [ 60 , 61 ].…”