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
Graft versus host disease(GVHD)is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases.Inflammatory cascade responses ...Graft versus host disease(GVHD)is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases.Inflammatory cascade responses and cellular immune reactions are the major factors underlying GVHD pathogenesis.Cells producing the cytokine,interleukin(IL)-21 are crucial players involved in injured tissues in GVHD patients.Besides T helper 17 cells,follicular T helper(Tfh)cells are a new source of IL-21 and play a vital role in GVHD pathogenesis.Tfh cell function is mostly regulated by T-follicular regulatory(Tfr)cells that are also located in the germinal center.This review highlights recent advances in the role of Tfh and Tfr cell function in GVHD pathogenesis.New insights are provided into the potential for clinical application in GVHD prevention and treatment.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.
基金This work was in part supported by the National Natural Science Foundation of China(81373156,81570587,81401324,81671611)Science and Technology Planning Project of Guangdong Province(2016A020215048,2014A030308005)+1 种基金Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology(2013A061401007)Guangdong Provincial International Cooperation Base of Science and Technology(Organ Transplantation)(2015B050501002),China.
文摘Graft versus host disease(GVHD)is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases.Inflammatory cascade responses and cellular immune reactions are the major factors underlying GVHD pathogenesis.Cells producing the cytokine,interleukin(IL)-21 are crucial players involved in injured tissues in GVHD patients.Besides T helper 17 cells,follicular T helper(Tfh)cells are a new source of IL-21 and play a vital role in GVHD pathogenesis.Tfh cell function is mostly regulated by T-follicular regulatory(Tfr)cells that are also located in the germinal center.This review highlights recent advances in the role of Tfh and Tfr cell function in GVHD pathogenesis.New insights are provided into the potential for clinical application in GVHD prevention and treatment.
