The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients fu...The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients functionally T cell deficient and hence highly susceptible to infections and tumor recurrence. Depletion is often accomplished through the use of broadly reactive antibodies, while functional impairment is typically achieved by pharmacological agents that require long-term administration (usually six months or more), have significant side effects, and may not result in tolerance (i.e., nonresponsiveness) of donor T cells to conditioning regimen-resistant host alloantigen-bearing cells. As our knowledge of immune system homeostasis has increased, cell populations with immune regulatory function have been identified and characterized. Although such cell populations are typically present in low frequencies, methods to isolate and expand these cells have permitted their supplementation to the donor graft or infusion late post-transplant in order to stifle GVHD. This review discusses the biology and preclinical proof of concept of GVHD models, along with GVHD outcomes that focus exclusively on immune regulatory cell therapies that have progressed to clinical testing.展开更多
Objective To investigate the effects of artesunatetreatment on chronic graft-versus-host disease(cGVHD). Methods Recipient BALB /c mice received8 × 106 bone marrow cells with 8 × 106 spleen cells fromB10D2 m...Objective To investigate the effects of artesunatetreatment on chronic graft-versus-host disease(cGVHD). Methods Recipient BALB /c mice received8 × 106 bone marrow cells with 8 × 106 spleen cells fromB10D2 mice. Artesunate solubilized in acetone was injectedintraperitoneally every day at a dose of 1 mg /kg onDay 28 after BMT. The clinical scores,survival and histopathologicaldamage were analyzed. The frequency ofTh17 and Tregs in PB and spleens from the mice wereevaluated by flow cytometry. In addition,CD4 + T cellsfrom the spleens of mice were cultured in vitro,thenstimulated with artesunate,the frequency of Th17 andTregs in these splenocytes were evaluated by flow cytometry.展开更多
基金supported by grants from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (R37 AI34495)National Heart, Lung, and Blood Institute, National Institutes of Health (R01 HL56067 and R01 HL11879)National Cancer Institute, National Institutes of Health (P01 CA142106 and P01 CA065493)
文摘The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients functionally T cell deficient and hence highly susceptible to infections and tumor recurrence. Depletion is often accomplished through the use of broadly reactive antibodies, while functional impairment is typically achieved by pharmacological agents that require long-term administration (usually six months or more), have significant side effects, and may not result in tolerance (i.e., nonresponsiveness) of donor T cells to conditioning regimen-resistant host alloantigen-bearing cells. As our knowledge of immune system homeostasis has increased, cell populations with immune regulatory function have been identified and characterized. Although such cell populations are typically present in low frequencies, methods to isolate and expand these cells have permitted their supplementation to the donor graft or infusion late post-transplant in order to stifle GVHD. This review discusses the biology and preclinical proof of concept of GVHD models, along with GVHD outcomes that focus exclusively on immune regulatory cell therapies that have progressed to clinical testing.
文摘Objective To investigate the effects of artesunatetreatment on chronic graft-versus-host disease(cGVHD). Methods Recipient BALB /c mice received8 × 106 bone marrow cells with 8 × 106 spleen cells fromB10D2 mice. Artesunate solubilized in acetone was injectedintraperitoneally every day at a dose of 1 mg /kg onDay 28 after BMT. The clinical scores,survival and histopathologicaldamage were analyzed. The frequency ofTh17 and Tregs in PB and spleens from the mice wereevaluated by flow cytometry. In addition,CD4 + T cellsfrom the spleens of mice were cultured in vitro,thenstimulated with artesunate,the frequency of Th17 andTregs in these splenocytes were evaluated by flow cytometry.
