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Transplant Success With T-Cell Technique

Modified Response May Combat Organ Rejection

Exhausting parts of the immune system might seem counterintuitive to medical advancement, but a new study from Northwestern Medicine suggests controlled dysfunction might be the key to combating chronic organ transplant rejection.

A team of Northwestern scientists led by M. Javeed Ansari, MBBS, assistant professor of Medicine-Nephrology and Surgery-Organ Transplantation, used a mouse model of chronic heart transplant rejection to study how the immune system can damage transplanted organs over time. While immunosuppressive medication makes rejection uncommon in the first year, many transplants, including 40 to 50 percent of kidneys, fail to function after five years.

Understanding and Exhausting T-Cell Response

Chronic transplant rejection is related to an ongoing response from the body’s immune system. This includes T-cells, which are white blood cells central to protecting the body from infection. Because the body recognizes transplants as foreign tissue, T-cells sometimes continue to target the new organ over time.

Using mice with impaired T-cells, the Northwestern scientists were able to show that when prevented from reaching their target, T-cells experience a form of dysfunction called T-cell exhaustion, thus protecting the transplant organ. The study showed that when the immune response is modified, a body can tolerate foreign organs, encouraging long-term transplant survival.

Targeting Cells for Prevention and Direction

With this knowledge, scientists can work toward developing a compound that induces T-cell exhaustion to protect transplant organs. Ultimately, Dr. Ansari and his team hope to specifically target the cells responding to the transplant, allowing the other white blood cells to continue to fight infections and cancers.

The study offers potential breakthroughs in the fields of infectious disease and cancer immunology as well, where T-cell exhaustion can be a serious concern for patients fighting infection. Using the same research, scientists may be able to guide rather than prevent immune responses to infection or tumors.