The Interactions of T Cells with Myeloid-Derived Suppressor Cells in Peripheral Blood Stem Cell Grafts
Qingdong Guan,
Scott G. Gilpin,
James Doerksen,
Lauren Bath,
Tracy Lam,
Yun Li,
Pascal Lambert,
Donna A. Wall
Affiliations
Qingdong Guan
Manitoba Blood and Marrow Transplant Program, Departments of Pediatrics and Child Health and Internal Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Scott G. Gilpin
Manitoba Blood and Marrow Transplant Program, Departments of Pediatrics and Child Health and Internal Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
James Doerksen
Manitoba Blood and Marrow Transplant Program, Departments of Pediatrics and Child Health and Internal Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Lauren Bath
Manitoba Blood and Marrow Transplant Program, Departments of Pediatrics and Child Health and Internal Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Tracy Lam
Manitoba Blood and Marrow Transplant Program, Departments of Pediatrics and Child Health and Internal Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Yun Li
Manitoba Blood and Marrow Transplant Program, Departments of Pediatrics and Child Health and Internal Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Pascal Lambert
Department of Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, MB R3A 1R9, Canada
Donna A. Wall
Manitoba Blood and Marrow Transplant Program, Departments of Pediatrics and Child Health and Internal Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
The interaction of myeloid-derived suppressor cells (MDSCs) with T cells within G-CSF-mobilized peripheral blood stem cell (PBSC) grafts in patients undergoing autologous or allogeneic hematopoietic stem cell transplantation remains to be elucidated. Through studying allo- and auto-PBSC grafts, we observed grafts containing large numbers of T cells and MDSCs with intergraft variability in their percentage and number. T cells from autologous grafts compared to allografts expressed relative higher percentages of inhibitory receptors PD-1, CTLA-4, TIM-3, LAG-3, TIGIT and BTLA. Autograft T cells had decreased cell proliferation and IFN-γ secretion, which supported the possible presence of T cell exhaustion. On the contrary, graft monocytic MDSCs (M-MDSCs) expressed multiple inhibitory receptor ligands, including PD-L1, CD86, Galectin-9, HVEM and CD155. The expression of inhibitory receptor ligands on M-MDSCs was correlated with their corresponding inhibitory receptors on T cells in the grafts. Isolated M-MDSCs had the ability to suppress T cell proliferation and IFN-γ secretion and/or promote Treg expansion. Blocking the PD-L1-PD-1 signaling pathway partially reversed the functions of M-MDSCs. Taken together, our data indicated that T cells and M-MDSCs in PBSC grafts express complementary inhibitory receptor–ligand pairing, which may impact the quality of immune recovery and clinical outcome post transplantation.
