BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a naturally occurring, heterogeneous population of highly immunosuppressive cells which expand in response to inflammatory conditions such as cancer. Although MDSCs develop after organ transplantation in immunosuppressed recipients, it is unknown if transplantation alone leads to MDSC development. We hypothesized that MDSCs can develop following the inflammatory response to transplantation.

METHODS: Kidney transplants were performed between C57BL/6 and BALB/c mice, without immunosuppression. Syngeneic and immunosuppressed mouse kidney transplant recipients were used as controls. Native nephrectomy was performed to confirm transplants were life-supporting. Mouse spleens, grafts, and blood were collected from euthanized animals and assessed for the development and function of MDSCs. Immunohistochemistry was performed to evaluate for intra-graft MDSCs. Alloantibody was identified by flow cytometry. Mixed lymphocyte reactions and co-culture assays were used to assess the suppressive capacity of CD11b+Gr-1+ MDSCs. and compared to tumor induced MDSCs.

RESULTS: Kidney transplant recipients of MHC-disparate grafts uniformly developed rejection, and alloantibody was detected at days 9-12. Syngeneic controls with native nephrectomy were sacrificed at 100 days with clinically normal kidney function. CD11b+Gr-1+ ti-MDSCs isolated from the spleens of MHC-disparate kidney transplant recipients were significantly expanded in the absence of immunosuppression, when compared to wild type and syngeneic controls. In co-culture, transplant induced MDSCs were suppressive of CD4+ T cell responses, but less so than tumor-induced MDSCs. Immunohistochemical analysis demonstrated a marked increase in splenic and intra-graft MDSCs after transplantation. In contrast, ATG treatment significantly reduced intrasplenic and intragraft MDCSs.

CONCLUSION: MDSCs developed in response to solid organ transplantation alone, in the absence of immunosuppression, which has not previously been shown. Transplantation induced MDSCs can suppress alloreactive responses and could be targeted for expansion with the goal of minimizing or avoiding immunosuppression in transplant recipients.

CITATION INFORMATION: Lee Y., Davila E., Bromberg J., Scalea J. Myeloid Derived Suppressor Cells Are Induced after Transplantation and Home to the Transplanted Kidney Am J Transplant. 2017;17 (suppl 3).

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