Date: Sunday, April 30, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Belatacept, a CD28-CD80/86 blocker, was approved by the FDA to provide immunosuppression without nephrotoxicity or cardiovascular and metabolic adverse effects. As part of our multi-center randomized clinical trial to investigate the role of belatacept-based early steroid withdrawal under T cell-depleting induction therapy in kidney transplant recipients (BEST Trial, clinicaltrials.gov #NCT01729494), we observed that acute rejection in belatacept treated patients frequently were refractory to standard antirejection therapy and were immunologically distinct from those treated with calcineurin inhibitor (CNI) therapy.
To further understand the nature of these rejections, we have serially characterized the emergence of activated T cells in PBMCs and in the kidney allograft using flow cytometry in belatacept-treated patients with and without rejection. Our data show that a substantial population of CD8+CD28lo effector/memory T cells (TEM) emerge in the blood and the renal allograft during rejection under belatacept, but not during CNI based therapy. These TEM cells also expressed high levels of CD38. Notably, in several belatacept-treated patients who were refractory to standard rejection therapy, we found that addition of an mTOR inhibitor decreased the frequency of CD8+CD28loCD38hi TEM cells in the peripheral blood that was also accompanied by histologic improvement on repeat allograft biopsy. Ongoing studies are examining the donor-specific alloreactivity and gene signatures of CD8+CD28loCD38hi TEM cells as well as the effects of mTOR inhibition on FoxP3+ regulatory T cells.
CITATION INFORMATION: Castro-Rojas C, Godarova A, Leino A, Alloway R, Jordan M, Woodle E, Hildeman D. mTOR Inhibition Diminishes Peripheral Blood CD8+CD28–CD38hi Effector/Memory T Cells and Facilitates Resolution of Belatacept-Refractory Kidney Rejection. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Castro-Rojas C, Godarova A, Leino A, Alloway R, Jordan M, Woodle E, Hildeman D. mTOR Inhibition Diminishes Peripheral Blood CD8+CD28–CD38hi Effector/Memory T Cells and Facilitates Resolution of Belatacept-Refractory Kidney Rejection. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/mtor-inhibition-diminishes-peripheral-blood-cd8cd28-cd38hi-effectormemory-t-cells-and-facilitates-resolution-of-belatacept-refractory-kidney-rejection/. Accessed August 4, 2020.
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