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Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients

in Science Translational Medicine

When a patient receives a transplant, a unique population of T lymphocytes emerges to reject the foreign organ. Immunosuppressive medication is therefore necessary to prevent rejection and protect the transplanted kidney. Previously, it had not been possible in humans to identify these specific T cells due to their vast number and diversity; furthermore, this population is unpredictable and distinct for each transplant patient and his or her organ donor. In this paper, we describe a new technique to identify these thousands of T cells before the time of kidney transplantation and then track them over time after transplant circulating in peripheral blood. We used this technique to study six kidney transplant recipients to investigate in a new way what happens to these cells when patients have different clinical outcomes. Some of the patients studied were part of a unique cohort who received combined kidney and bone marrow transplants from the same donor in order to induce tolerance and accept their grafts without life-long immunosuppressive medication. Our T cell tracking analysis provided a deeper understanding of the mechanism of tolerance in these patients. This new technique provides a window into the fate of these donor-specific T cells and has potential as a possible biomarker for predicting and identifying rejection and tolerance in different types of transplant patients. 

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