Newswise — DUARTE, California — The National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) has awarded a $2.2 million grant to help City of Hope researchers explore the underlying mechanisms of graft-versus-host disease, the leading cause of long-term sickness and death following transplantation of bone marrow cells from a donor. The grant, awarded to Defu Zeng, M.D., a professor of diabetes immunology and hematopoietic cell transplantation at the Beckman Research Institute of City of Hope, will be used by researchers to study the interactions of immune cells known as T cells and B cells during the development of GVHD.
“If successful, this research will provide new insights into the mechanisms of chronic GVHD development and may identify targets to prevent autoimmunity,” Zeng said.
Transplantation of bone marrow, more formally referred to as hematopoietic cell transplantation, can be a curative therapy for cancers of the blood or bone marrow, including lymphoma, multiple myeloma and leukemia; it also can be a treatment for severe autoimmune diseases.
The autologous version of the procedure uses cells from the patient; the allogeneic version uses cells from a donor, creating the potential for the patient’s immune system to reject the donated tissue. In order for the donor bone marrow cells to engraft in the recipient, total body irradiation and/or high dose chemotherapy is used to wipe out the patient’s immune system. This creates a situation in which donor immune cells can attack a patient’s tissues in the gut, liver and lung, among other sites. This attack causes a painful disease called GVHD. Although death immediately following allogeneic transplantation has markedly decreased over the years, little progress has been made in reducing the risks of chronic GVHD, a painful complication in which the transplanted donor T and B cells work together to attack the patient’s tissues.
Zeng is a leader in the field of treating autoimmune diseases through the induction of mixed chimerism, in which donor cells are transplanted into a patient with mild conditioning, such that donor and patient immune cells and blood cells co-exist harmoniously without causing GVHD. He is also an expert in designing mouse models of chronic GVHD that reflect the development of the disease in humans. Using these mice, Zeng and his team of researchers at City of Hope have shown that disruption of interactions between donor T and B cells can prevent chronic GVHD; the grant will allow them to expand on that work.
“The proposed studies will provide new insights into how donor CD4-positive T and B cells interact to induce and perpetuate chronic GVHD and will lead to the development of novel regimens for prevention and treatment of chronic GVHD,” Zeng said.
Research reported in this publication was supported by the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Grant Number R01 AI066008. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.