Scientists in the lab of Defu Zeng, Ph.D., have found that certain T cells may play a key role in a potentially deadly complication in hematopoietic cell transplants involving unrelated donors. The findings may have implications for treatment of inflammatory autoimmune diseases.
Graft-versus-host disease, or GVHD, is among the most common and dangerous side effects for patients undergoing allogeneic hematopoietic cell transplantation, or HCT. Physicians perform allogeneic transplants to treat patients with certain blood-based cancers. The transplants use stem cells from a healthy donor to create a new immune system in these patients. Unfortunately, sometimes immune cells from the donor attack the patient’s own tissues and organs as if they were foreign — resulting in GVHD.
|Tangsheng Yi, left, and Defu Zeng (Photo by Dongchang Zhao)|
A recently discovered type of helper T cells, called Th17 cells, appear to try to counteract acute GVHD, according to published lab research by City of Hope’s Tangsheng Yi, a graduate student in Zeng’s lab. Yi is the main author on the paper, which was published in the Sept. 1 issue of Blood.
The findings signal that Th17 cells’ role is more complicated than scientists suspected.
“Th17 cells have been shown to play a critical role in driving inflammatory responses in autoimmune diseases, such as multiple sclerosis and psoriasis,” Yi said. Th17 cells produce a protein called interleukin-17, or IL-17. Some scientists have proposed neutralizing IL-17 as a way to suppress inflammation.
“Pharmaceutical companies are developing drugs to do this to treat autoimmune diseases,” Yi said.
But in GVHD, Th17 cells and IL-17 protect against a dangerous immune response, and Zeng said that should signal caution. “Our data clearly indicate that neutralizing IL-17 will not be good for treating acute GVHD,” said Zeng, assistant professor in the Division of Diabetes, Endocrinology & Metabolism and the Department of Hematology & Hematopoietic Cell Transplantation. “It is a good warning.”
The scientists conducted their research by performing transplants on special lab mice that are engineered to produce no Th17 cells. Without these cells, they saw far greater than normal numbers of other helper T cells known as Th1 cells, as well as more of a powerful protein called interferon-gamma. The Th1 cells and interferon-gamma prompted exacerbated, acute GVHD.
The researchers concluded that Th17 seems to keep inflammation-causing Th1 cells in check.
Today, the team is trying strategies to push Th17 production and testing whether neutralizing interferon-gamma can ease acute GVHD.
Zeng also is collaborating with cancer biologist Hua Yu, Ph.D., to understand the role of Th17 in regulating tumor growth.
The Th17 research may be important for the thousands of patients who undergo HCT and is impressive work for a graduate student, said Zeng.
Not long after entering the City of Hope Graduate School of Biological Sciences, Yi was struck by the impact of HCT and the therapeutic potential of work under way in Zeng’s lab. “It perfectly fit what I hope and want to do,” he said.
Yi was inspired to pursue the research through a guest in the graduate school’s Leading-edge Lecture Series, which allows students to invite outside professors to speak. Yi invited Abul Abbas, M.D., professor and chair of pathology from the University of California, San Francisco, who is an expert on IL-17 and cellular immunity. “After a whole day’s interaction with him, I felt interested in IL-17 — and he said it would be very interesting and critical to study IL-17 in HCT,” Yi said. “We made the right choice.”