Doctors at the University of Pittsburgh reported that three liver transplant recipients remained off immunosuppressant drugs for an average of three years after receiving infusions of donor-derived regulatory dendritic cells.
The little clinical trial, published Friday in Nature Communications, involved 13 living liver transplant patients who received a dose of their donor’s regulatory dendritic cells one week before surgery.
Participants were initially placed on standard anti-rejection therapy, then monitored for a year before attempts to taper medications began.
Of the eight patients deemed eligible for drug withdrawal based on immune tolerance markers, four stopped taking immunosuppressants completely; one later resumed the drugs, while three remained drug-free through the study’s conclusion.
The approach aims to eliminate lifelong immunosuppression, which increases infection and cancer risks and can cause diabetes and kidney damage over time.
Researchers used regulatory dendritic cells — immune cells that can signal other cells to reduce reactivity — derived from donor white blood cells and expanded in the lab.
The theory is that pre-transplant exposure to these donor cells trains the recipient’s immune system to accept the new liver as self rather than foreign tissue.
Livers were selected for the trial because they are generally better tolerated by the immune system and can be donated while living due to their regenerative capacity.
Living donor liver transplants allow recipients to regain function from partial organs that regrow, often treating conditions like alcohol-associated or metabolic liver disease.
Previous attempts to induce tolerance used regulatory T cells from donors, but this study is among the first to test regulatory dendritic cells in human liver transplantation.
The researchers emphasized the results are preliminary but suggest a feasible and safe path toward reducing medication dependence for select transplant recipients.
How the dendritic cell infusion process worked in the trial
Each participant received a single infusion of donor-derived regulatory dendritic cells harvested from white blood cells and processed in a laboratory setting.
The infusion occurred approximately seven days before the living donor liver transplant procedure.
Patients then underwent standard transplant surgery followed by conventional immunosuppression to prevent early rejection.
Immune monitoring over the subsequent year identified which recipients had developed sufficient tolerance to attempt drug withdrawal.
Why researchers focused on liver transplants for this approach
The study team chose living donor liver transplants because livers provoke weaker immune responses compared to other organs, based on prior clinical observations.
the liver’s unique ability to regenerate allows donors to safely contribute a lobe that regrows to full size within months.
This regenerative property also benefits recipients, as the transplanted partial liver can expand to meet metabolic demands over time.
These biological factors made the liver an ideal candidate for initial testing of immune tolerance strategies in humans.
What the drugs patients stopped taking actually do in the body
Immunosuppressants prevent organ rejection by broadly inhibiting immune cell activity, but this action also diminishes defenses against viruses, bacteria and fungi.
Long-term use is associated with metabolic side effects, including new-onset diabetes after transplant and progressive kidney injury.
Some recipients develop skin cancers or lymphoproliferative disorders due to chronic immune suppression.
By reducing or eliminating these medications, the trial sought to lower cumulative toxicity while maintaining graft acceptance.
What remains unknown about the long-term effects of this method
The study did not track patients beyond three years, so We see unclear whether tolerance will persist indefinitely or if late rejection could occur.
It is also unknown whether the approach would perform for organs other than the liver, such as kidneys or hearts, which are less tolerable by nature.
Larger, longer trials are needed to determine which patients are most likely to succeed with drug withdrawal and whether dosing or timing adjustments improve outcomes.
How many patients in the trial were able to stop taking immunosuppressant drugs?
Three patients stopped taking immunosuppressant drugs and remained off them for an average of three years; a fourth patient initially stopped but later resumed medication.
What type of cells were used in the experimental treatment?
The treatment used regulatory dendritic cells derived from the donor’s white blood cells, which were generated in a lab before infusion.