Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: The obesity epidemic has expanded rapidly over the last decade. Our program is developing a novel clinical protocol using expanded autologous regulatory T cell (Treg) infusions to induce tolerance in transplantation. The reduced number and impaired function of circulating Tregs in obese are specially challenging for manufacturing functionally competent suppressive Treg cells for clinical use.
*Methods: We enrolled 15 obese (BMI>30) and 15 non-obese patients (BMI<30) with ERSD. We analyzed the Treg phenotype with the following markers: CD4, FoxP3, CD25, CD127, Helios, Eomes, CD36, GLUT-1, OX40, GITR, 4-1BB, TIGIT, CD226, CTLA-4, ICOS, PD1, CD39, CD49d, CCR4, CCR2, CCR7 and CXCR3. We also assessed the expansion and suppressor function of isolated Treg cells.
*Results: We found reduced baseline numbers and function of Treg cells in the obese compared to non-obese ESRD patients. These results correlate with different expression rate levels of the glucose receptor GLUT1 and the fatty acid translocase CD36, thus supporting the metabolic dysfunction as a potential contributor to the altered obese ESRD Treg cells. We observed a delay in the expansion rates of obese Treg cells. However, this delay does not prevent reaching adequate numbers of functional cells for adoptive Treg immunotherapy.
*Conclusions: We have characterized phenotypic and functional alterations in obese compared to non-obese Treg cells in ESRD patients. The standard manufacturing protocol using IL2, CD3/CD28 microbeads and Rapamycin can overcome these alterations.
To cite this abstract in AMA style:Marti F, Ruffing A, Chacon E, Turcios L, Valvi D, Gonzalez J, Gedaly R. Challenges in Manufacturing Clinically Competent Regulatory T Cells from Obese Renal Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/challenges-in-manufacturing-clinically-competent-regulatory-t-cells-from-obese-renal-transplant-recipients/. Accessed March 8, 2021.
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