In Vivo Mobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid-Derived Suppressor Cells

Area of Science:

• Immunology
• Transplantation Biology

Background:

• Myeloid-derived suppressor cells (MDSCs) are increasingly recognized for their role in immune suppression and transplant tolerance in animal models.
• Identifying and characterizing MDSCs in nonhuman primates is crucial for translating these findings to clinical applications.

Purpose of the Study:

• To identify and characterize monocytic MDSCs in rhesus macaques.
• To evaluate the in vitro immunomodulatory functions of these MDSCs.
• To assess the potential of MDSCs for therapeutic applications in transplantation.

Main Methods:

• Flow cytometry was used to identify and quantify monocytic MDSCs (CD3(-)CD20(-)HLA-DR(-)CD14(+)CD33(+)CD11b(+)) in peripheral blood of rhesus macaques.
• MDSC incidence was modulated using granulocyte-macrophage colony-stimulating factor and granulocyte CSF.
• Functional assays involved co-culturing isolated MDSCs with autologous T cells stimulated with anti-CD3 and anti-CD28 antibodies to assess T cell proliferation, cytokine secretion, and regulatory T cell expansion.

Main Results:

• Putative monocytic MDSCs were identified in rhesus macaque peripheral blood, comprising 2.1% ± 1.7% of lin(-)HLA-DR(-) PBMCs.
• MDSC numbers increased significantly upon stimulation with CSF (5.3% ± 3.4%).
• Isolated MDSCs suppressed CD4(+) and CD8(+) T cell proliferation and cytokine production, enhanced regulatory T cell (Treg) expansion, and inhibited memory T cell proliferation.
• Arginase-1 inhibition partially reversed MDSC-mediated suppression of CD8(+) T cell proliferation.

Conclusions:

• Functional monocytic MDSCs can be identified and isolated from rhesus macaques.
• These MDSCs exhibit potent immunosuppressive properties, including inhibition of effector T cells and promotion of Tregs.
• Isolated MDSCs hold promise as a cellular therapy for inducing transplant tolerance.