In graft-versus-host disease, or GVHD, transplanted immune cells from a donor attack the tissue of a hematopoietic cell transplant patient. Scientists thought that all the transplanted donor immune cells — T cells — could cause GVHD, but City of Hope researchers have found compelling evidence to the contrary.
Writing in the Sept. 1 issue of Blood, City of Hope researchers showed that certain T cells actually can suppress GVHD. The important finding offers hope that these T cells might someday be used to treat GVHD. The condition is the most common and potentially deadly side effect for patients receiving hematopoietic cell transplantation, or HCT, using cells from unrelated donors.
HCT is used to treat blood cancers including leukemia, lymphoma and multiple myeloma.
|Defu Zeng, front, and Dongchang Zhao (Photo by p.cunningham)|
Defu Zeng, M.D., and postdoctoral fellow Dongchang Zhao, M.D., Ph.D., of the Division of Diabetes, Endocrinology & Metabolism and the Department of Hematology & Hematopoietic Cell Transplantation, observed in the lab that donor T cells can differentiate into two populations after bone marrow transplantation.
“One is pathogenic, or ‘bad,’ and can cause GVHD,” explained Zeng. “The other one is ‘good’ and can regulate and suppress GVHD. We have identified a marker for those good T cells, termed ‘CD103.’”
“It is the first time we’ve identified this regulatory T cell population in HCT recipients,” Zeng added.
They saw firsthand in the lab how these T cells battle HCT. Studying genetically identical mice that had undergone HCT and developed GVHD, they infused “good” CD103-expressing T cells from one mouse into other mice. They saw that the infusion of T cells markedly improved severe GVHD.
The scientists believe it would be possible to isolate these CD103-expressing “good” T cells from a patient with chronic GVHD, expand them in the laboratory, and then reinfuse them back into the patient as a therapy for chronic GVHD. Currently, physicians have no effective therapy for chronic GVHD.
“The important discovery here is that before, we thought that all the donor T cells we infused were bad for GVHD; now what we’ve found is that among those ‘bad’ cells, there are some ‘good’ cells that can be used to control their ‘bad’ siblings,” Zeng explained.
“A lot of papers have been published showing that natural Treg cells can prevent GVHD if they are infused before the disease develops, but natural Treg cells are ineffective in treating ongoing GVHD,” Zeng continued. “This is the first important study showing that Treg cells — if they are activated in the body — can be used to ameliorate ongoing GVHD.”
Zeng said further study is needed to replicate the findings in human clinical trials. The National Marrow Donor Program facilitates more than 1,000 matching, unrelated donor HCT procedures in the United States every year.