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Myeloid-derived Suppressor Cells Recruit CD4(+)/Foxp3(+) Regulatory T Cells in a Murine Cardiac Allograft. 2016

T Nakamura, and T Nakao, and E Ashihara, and N Yoshimura
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.

BACKGROUND 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. OBJECTIVE 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007108 Immune Tolerance The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. Immunosuppression (Physiology),Immunosuppressions (Physiology),Tolerance, Immune
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D000072737 Myeloid-Derived Suppressor Cells A heterogeneous, immature population of myeloid cells that can suppress the activity of T-CELLS and NATURAL KILLER CELLS in the INNATE IMMUNE RESPONSE and ADAPTIVE IMMUNE RESPONSE. They play important roles in ONCOGENESIS; INFLAMMATION; and INFECTION. MDSC,Myeloid Derived Suppressor Cell,MDSCs,Cell, Myeloid-Derived Suppressor,Cells, Myeloid-Derived Suppressor,Myeloid Derived Suppressor Cells,Myeloid-Derived Suppressor Cell,Suppressor Cell, Myeloid-Derived,Suppressor Cells, Myeloid-Derived
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014184 Transplantation, Homologous Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals. Transplantation, Allogeneic,Allogeneic Grafting,Allogeneic Transplantation,Allografting,Homografting,Homologous Transplantation,Grafting, Allogeneic
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016027 Heart Transplantation The transference of a heart from one human or animal to another. Cardiac Transplantation,Grafting, Heart,Transplantation, Cardiac,Transplantation, Heart,Cardiac Transplantations,Graftings, Heart,Heart Grafting,Heart Graftings,Heart Transplantations,Transplantations, Cardiac,Transplantations, Heart
D050378 T-Lymphocytes, Regulatory CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells. Regulatory T Cell,Regulatory T-Cell,Regulatory T-Lymphocyte,Regulatory T-Lymphocytes,Suppressor T-Lymphocytes, Naturally-Occurring,T-Cells, Regulatory,Th3 Cells,Tr1 Cell,Treg Cell,Regulatory T-Cells,Suppressor T-Cells, Naturally-Occurring,Tr1 Cells,Treg Cells,Cell, Regulatory T,Cell, Th3,Cell, Tr1,Cell, Treg,Cells, Regulatory T,Cells, Th3,Cells, Tr1,Cells, Treg,Naturally-Occurring Suppressor T-Cell,Naturally-Occurring Suppressor T-Cells,Naturally-Occurring Suppressor T-Lymphocyte,Naturally-Occurring Suppressor T-Lymphocytes,Regulatory T Cells,Regulatory T Lymphocyte,Regulatory T Lymphocytes,Suppressor T Cells, Naturally Occurring,Suppressor T Lymphocytes, Naturally Occurring,Suppressor T-Cell, Naturally-Occurring,Suppressor T-Lymphocyte, Naturally-Occurring,T Cell, Regulatory,T Cells, Regulatory,T Lymphocytes, Regulatory,T-Cell, Naturally-Occurring Suppressor,T-Cells, Naturally-Occurring Suppressor,T-Lymphocyte, Regulatory,Th3 Cell

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