Bo Tang1, Hanyun Ren2, Huihui Liu1, Yongjin Shi1, Wei Liu1, Yujun Dong1, Yue Yin1, Shengchao Miao1. 1. Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China. 2. Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China. renhy0813@163.com.
Abstract
OBJECTIVE: Our preview study found that CCR5 blockade combined with cyclosporine A could attenuate the severity of liver GVHD. But the potential immunological mechanisms have not yet been explored. So our present study was designed to clarify the potential immunological mechanisms in mouse models after allo-HSCT. METHODS: Firstly, we detected donor T cells homing to target organs, and analyzed the specific effector subsets in liver. Additionally, we assessed antigen-presenting cells (APCs), especially DCs and CD4+ T cells differentiation in secondary lymphoid organs. RESULTS: Data showed that MVC combined with CsA reduced donor T cells migration to target organs in vivo. MVC and CsA treatment reduced the amount of donor T cells in the absolute numbers, also in donor CD4+ and CD8+ T cells by targeting at CCR5. And MVC co-injected with CsA was capable of slightly suppressing DC maturation, and reduced the percentage of Th1 and Th17 mainly by noncompetitive combination of CCR5. CONCLUSION: Combined use of MVC and CsA was effective in attenuating liver GVHD in murine model. It can suppress DC maturation, affect T cells differentiation, and reduce donor T cells homing to target organs. This may offer a novel therapeutic perspective approach for clinical liver GVHD after allo-HSCT.
OBJECTIVE: Our preview study found that CCR5 blockade combined with cyclosporine A could attenuate the severity of liver GVHD. But the potential immunological mechanisms have not yet been explored. So our present study was designed to clarify the potential immunological mechanisms in mouse models after allo-HSCT. METHODS: Firstly, we detected donor T cells homing to target organs, and analyzed the specific effector subsets in liver. Additionally, we assessed antigen-presenting cells (APCs), especially DCs and CD4+ T cells differentiation in secondary lymphoid organs. RESULTS: Data showed that MVC combined with CsA reduced donor T cells migration to target organs in vivo. MVC and CsA treatment reduced the amount of donor T cells in the absolute numbers, also in donor CD4+ and CD8+ T cells by targeting at CCR5. And MVC co-injected with CsA was capable of slightly suppressing DC maturation, and reduced the percentage of Th1 and Th17 mainly by noncompetitive combination of CCR5. CONCLUSION: Combined use of MVC and CsA was effective in attenuating liver GVHD in murine model. It can suppress DC maturation, affect T cells differentiation, and reduce donor T cells homing to target organs. This may offer a novel therapeutic perspective approach for clinical liver GVHD after allo-HSCT.
Entities:
Keywords:
CCR5 blockade; Graft-versus-host disease; Murine model; T cells
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