T Nakamura1, T Nakao2, E Ashihara3, N Yoshimura2. 1. Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto-prefecture, Japan. Electronic address: tsukasa@koto.kpu-m.ac.jp. 2. Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto-prefecture, Japan. 3. Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, 5 Nakauchi, Yamashina-ku, Kyoto, Japan.
Abstract
INTRODUCTION: Myeloid-derived suppressor cells (MDSCs) play an important role in regulating allograft rejection in organ transplantation. On the other hand, CD3(+)/CD4(+)/FOXP3(+) regulatory T cells (Tregs) also are of vital importance in immunological tolerance. We previously revealed that adoptive transfer of MDSCs recruited Tregs in the spleen. However, it is still uncertain whether MDSCs are capable of recruiting Tregs to an allograft in vivo. OBJECTIVES: We conducted adoptive transfer experiments of MDSCs to clarify the effects of MDSCs on Tregs in vivo. METHODS: Gr-1(+)/CD11b(+) MDSCs were isolated from rapamycin-treated cardiac transplant (CTx) recipients (3 mg/kg, intraperitoneally on postoperative days [POD] 0, 2, 4, and 6) on POD 7 by magnetic-activated cell sorting (purity >95%). In murine heterotopic cardiac transplantation, 2 × 10(6) MDSCs were transferred into the graft aorta 5 minutes before reperfusion. RESULTS: Flow cytometric analyses of a cardiac allograft on POD 7 showed that MDSCs derived from rapamycin-treated CTx mice (MDSCs-Rap) transfer led to significant recruitment of Tregs compared with a PBS-injected allograft. The level of programmed death ligand-1 (PD-L1) on MDSCs-Rap was higher than those from non-treated recipients. Furthermore, pathological findings also confirmed accumulation of Foxp3(+) Tregs in an allograft. CONCLUSION: Induced PD-L1 on MDSCs might result in recruitment of Tregs. These results suggested that functional MDSCs possessed an ability to induce Tregs in a cardiac allograft and developed a tendency to immunological tolerance.
INTRODUCTION: Myeloid-derived suppressor cells (MDSCs) play an important role in regulating allograft rejection in organ transplantation. On the other hand, CD3(+)/CD4(+)/FOXP3(+) regulatory T cells (Tregs) also are of vital importance in immunological tolerance. We previously revealed that adoptive transfer of MDSCs recruited Tregs in the spleen. However, it is still uncertain whether MDSCs are capable of recruiting Tregs to an allograft in vivo. OBJECTIVES: We conducted adoptive transfer experiments of MDSCs to clarify the effects of MDSCs on Tregs in vivo. METHODS: Gr-1(+)/CD11b(+) MDSCs were isolated from rapamycin-treated cardiac transplant (CTx) recipients (3 mg/kg, intraperitoneally on postoperative days [POD] 0, 2, 4, and 6) on POD 7 by magnetic-activated cell sorting (purity >95%). In murine heterotopic cardiac transplantation, 2 × 10(6) MDSCs were transferred into the graft aorta 5 minutes before reperfusion. RESULTS: Flow cytometric analyses of a cardiac allograft on POD 7 showed that MDSCs derived from rapamycin-treated CTx mice (MDSCs-Rap) transfer led to significant recruitment of Tregs compared with a PBS-injected allograft. The level of programmed death ligand-1 (PD-L1) on MDSCs-Rap was higher than those from non-treated recipients. Furthermore, pathological findings also confirmed accumulation of Foxp3(+) Tregs in an allograft. CONCLUSION: Induced PD-L1 on MDSCs might result in recruitment of Tregs. These results suggested that functional MDSCs possessed an ability to induce Tregs in a cardiac allograft and developed a tendency to immunological tolerance.
Authors: Andreas Schroeter; Maximilian J Roesel; Tomohisa Matsunaga; Yao Xiao; Hao Zhou; Stefan G Tullius Journal: Front Immunol Date: 2022-07-06 Impact factor: 8.786