*Purpose: Myeloid-derived suppressor cells (MDSCs) inhibit T cell responses and may provide a pathway towards tolerance. Granulocyte-colony stimulating factor (GCSF) is used in clinical practice for leukopenia and is known to mobilize regulatory T cells (Tregs) and MDSCs. We aimed to evaluate the potential for GCSF-induced MDSCs to control allogeneic responses in a cardiac transplant model.

*Methods: Allogeneic heart transplants were performed between C57BL/6 and BALB/c mice. Mouse recombinant GCSF (200 ng/kg/d i.p. x 4d) was administered in naive or transplant recipients. CD11b⁺Gr-1⁺ cells were sorted and injected on the day of transplant (5 × 10⁶ cells i.v./mouse). Anti‐mouse Gr‐1 monoclonal antibody was used to deplete MDSCs (100 ug/kg). Proliferation assays assessed suppressive activity of MDSCs and fluorescent immunohistochemical staining was used to detect migrated MDSCs.

*Results: GCSF administration markedly increased the number and percentage (2.5%/increase by 15%) of CD11b⁺Gr-1⁺ MDSC in spleen. GCSF MDSCS were predominantly of the CD11b⁺Ly6G⁺Ly6C^low polymorphonuclear MDSC (PMN-MDSC) subset, rather than CD11b⁺Ly6G^–Ly6C^high monocytic MDSC (M-MDSC) subset (PMN vs M; 60 %/5 %). GCSF MDSCs suppressed CD4⁺ T cell proliferation in vitro. GCSF MDSCs accumulated within transplanted cardiac grafts but not found in naïve heart. In costimulatory blockade model, GCSF MDSC adoptive transfer led to markedly prolonged cardiac graft survival (132 days) when compared with adoptive transfer of MDSCs expanded by tumor (86 days). In contrast, MDSC depletion dramatically decreased graft survival time (11 days).

*Conclusions: Expansion of MDSCs by GCSF and their recruitment to cardiac allografts significantly improved allograft survival. Our results suggest that GCSF-mediated augmentation of MDSCs may be a new and important strategy to achieve immune tolerance in organ transplantation.

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