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Donor T cells change the fate of stem cells in transplantation

When a transplant patient suffers complications such as graft rejection or graft-versus-host disease, physicians attempt to stop the body's immune response by targeting a patient's T cells.

In a new study, University of Illinois at Chicago College of Medicine researchers suggest there may be a way to prevent these complications before they occur. The study was published July 1 in the journal Blood.

Previous studies by these researchers found that T cells are stimulated by blood stem cells -- immature cells that have yet to differentiate into the various cell types of the blood.

In the new study, the researchers report finding unexpected two-way communication and stimulation between blood stem cells and T cells.

In laboratory and animal models, the UIC researchers showed that alloreactive T cells change the fate of blood stem cells and may themselves stimulate a strong immune response.

"Knowing what mechanisms cause this change in stem cells would allow us to test immunosuppressive drugs and different T cell subsets, potentially preventing or reducing graft-versus-host disease or rejection," said Dr. Damiano Rondelli, associate professor of hematology at UIC and lead author of the study.

Graft-versus-host disease occurs when white blood cells from the donor attack tissues of the recipient. It is a very serious complication after stem cell transplantation from related or unrelated donors and may represent a cause of death in 30 to 50 percent of patients.

Graft rejection occurs when the immune system of the recipient rejects the donated graft. It is the opposite of graft-versus-host disease, but the mechanisms are the same.

Rondelli suggests that a loop occurs between stem cells and the donor T cells, causing them to grow and become immune-stimulating cells, called antigen-presenting cells. These new cells stimulate more T cells, and they recruit new stem cells to become more antigen-presenting cells. The more they activate each other, the more the T cell response grows.

"The idea that graft-versus-host disease and rejection can be related to stem cell function is intriguing," said Rondelli. "We know that by blocking some molecules we might stop these complications, which may translate into better outcomes for transplant patients."

Sherri McGinnis Gonzalez | EurekAlert!
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