Preventing Transplant Rejection: Researchers Identify Troublemaker T-Cells to Target for Organ Acceptance

March 4, 2024

Organ transplantation saves lives, but getting a new organ doesn't guarantee survival. Even on immunosuppressive medications, rejection of transplanted organs happens in up to 30% of patients, depending on the organ.

Recently, however, researchers from Houston Methodist Hospital identified a "troublesome" subset of T-cells in transplant recipients that may prove to be an effective therapeutic target to prevent transplant rejection.

Wenhao Chen, Ph.D., associate professor of Transplant Immunology with the Houston Methodist Research Institute, and his team used single-cell RNA sequencing to analyze the CD4+ T-cell response in transplantation scenarios. They identified a subset of CD4+ T-cells that acts like stem cells and continuously generates functionally mature effector T-cells that attack transplanted organs.

The groundbreaking research, recently published in the journal Nature Immunology, also describes the mechanism behind what directs that T-cell response in animal transplant models.

The team discovered that the transcription factor IRF4 is required for T-cells in that subset to become those organ-attacking effector T-cells. According to Dr. Chen, IRF4 is what needs to be targeted to solve the problem of transplant rejection or to develop an autoimmunity cure.

"T-cells play a central role in fighting infections and cancer, but they are also the key players in mediating autoimmune diseases and transplant rejection," Dr. Chen said. "Our study demonstrated that IRF4 is a master regulator of T-cell function, a discovery that will allow development of innovative therapies for patients with chronic infections, cancers, autoimmune diseases and transplanted organs."

Eliminating undesired CD4+ T-cell responses that could potentially lead to the loss of transplanted organs could eventually apply to all transplant patients, he said of this discovery.

After previous research on the challenge, Dr. Chen called how to therapeutically inhibit IRF4 "the Nobel-prize winning question." Most autoimmune diseases and transplant rejection will be solved, he said, "If we can find a way to inhibit IRF4 as desired in activated T-cells."

Now, the Nature publication should stir more interest.

"This revelation about the true 'troublemaker' within the CD4+ T cell population is just the tip of the iceberg," said Dr. Chen. "I sincerely hope that our findings garner widespread attention, motivating both researchers and patients to recognize the significance of targeting these 'troublemakers.'

To learn more about this research, click here to read the full article in our sister publication, Methodology.

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