Session Name: Immunosuppression Preclinical Studies
Session Date & Time: None. Available on demand.
*Purpose: Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells derived from bone marrow with immunosuppressive effect, which contribute to the establishment of transplant immune tolerance. Obtaining a sufficient number of MDSCs with potent suppressive function and good stability is a prerequisite for their clinical transformation and application. Our research found that transforming growth factor-beta (TGF-b) induced MDSCs with potent suppressive function promoted transplant immune tolerance.
*Methods: In vitro, we used mouse bone marrow cells as precursor cells for the induction of MDSCs, which obtained by TGF-b combined with GM-CSF, a growth factor stimulating the proliferation and differentiation of bone marrow cells. Flow cytometry detected the phenotype of induced MDSCs, and the immunosuppressive function and underlying cellular and molecular mechanism of these cells were explored by mixed lymphocyte culture and mouse skin transplantation model.
*Results: Compared with GM-CSF treatment alone, TGF-b combined with GM-CSF could induce more MDSCs, which have a stronger function of inhibiting activated CD4+ and CD8+ T cells. In addition, TGF-b induced MDSCs expressed higher levels of PD-L1. We further found that TGF-b induced MDSCs promoted the production of Tregs, and upregulated the expression of a variety of immunosuppressive molecules. Finally, adoptive transfer of these cells significantly prolonged the survival of allograft and promoted transplant immune tolerance.
*Conclusions: These results indicated that TGF-b combined with GM-CSF is an efficient and stable protocol to induce MDSCs in vitro. TGF-b induced MDSCs play a stronger immunosuppressive effect though inducing the production of Tregs and the expression of immune effector molecules. We firmly believe that TGF-b induced MDSCs combined with immunosuppressants are promising to further prolong the survival of allograft and promote transplant immune tolerance.
To cite this abstract in AMA style:Zhang F. Transforming Growth Factor-Beta Induced Myeloid-Derived Suppressor Cells Promote Transplant Immune Tolerance [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/transforming-growth-factor-beta-induced-myeloid-derived-suppressor-cells-promote-transplant-immune-tolerance/. Accessed June 11, 2021.
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