Evaluating T Cell Repopulation Post Alemtuzumab Induction with a Belatacept-Based Regimen.
Department of Surgery, Duke University, Durham, NC
Meeting: 2017 American Transplant Congress
Abstract number: B3
Keywords: Immunosuppression, Induction therapy, T cells
Session Information
Session Name: Poster Session B: Acute and Chronic Rejection
Session Type: Poster Session
Date: Sunday, April 30, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
We reported that alemtuzumab induction followed by belatacept-sirolimus based immunosuppression effectively prevents costimulation blockade resistant rejection (CoBRR). This study investigates the phenotypic characteristics of repopulating T cells post-depletion, specifically examining recent thymic emigrants (RTEs) and T cells from the mesentery.
The T cell repopulation of 20 patients treated with alemtuzumab induction followed by a belatacept/sirolimus based regimen was analyzed for 36 months post-transplantation by flow cytometry. The CD4+ and CD8+ RTEs were defined as CD31 expressing cells, while mesenteric T cells were characterized by surface expression of CD103. Naïve and memory phenotypes were defined using CCR7/CD45RA as follows: TC (CCR7+CD45RA–), Tnaive (CCR7+CD45RA+), TEMRA (CCR7–CD45RA+), and TEM (CCR7–CD45RA–).
Lymphocyte depletion was achieved post-transplantation using alemtuzumab induction. A significant increase of CD4+ RTEs (43±23 to 72±26.4%, p=0.0001) during post-depletion homeostatic proliferation was observed when compared to baseline levels (28.69±12.75%); the phenotype of these RTEs was primarily Tnaive cells. In contrast, non-RTE CD4+ cells were significantly reduced post-transplantation (p=0.0001). Prior to transplant, CD8+ cells were predominantly CD31+ (77.73±9.7%) characterized largely as TEMRA (33.5±14.2%) and TEM cells (31.95±13.17%). The frequency of CD31+CD8+ cells increased above baseline significantly post-transplantation (82.2±23.7 to 90.8±10.5%); this persisted 36 months. Initially, CD8+CD31+ cells were largely TEMRA cells in the first 2 months. However, thereafter Tnaive cells increased as the predominant subset (p=0.0074). In contrast, the frequency of CD8+CD31+ TEM cells were reduced (p=0.007). Unlike RTEs, CD4+CD103+ and CD8+CD103+ cells were resistant to depletional induction and had increased during early repopulation returning to baseline levels by 6 months post-transplant. However, a large proportion of CD8+CD103+ cells were Tnaive cells during repopulation.
In summary, patients treated with alemtuzumab induction followed by belatacept/sirolimus maintenance immunosuppression demonstrate remarkable CD31+ RTEs repopulation primarily of Tnaive cells. Although mesenteric T cells appear to be resistant to depletional induction, the CD8+CD103+ cells are largely Tnaive cells. This unique repertoire of RTEs are CD28+ and thus may be sensitive targets for belatacept in controlling the CoBRR after depletional induction.
CITATION INFORMATION: Bendersky V, Xu H, Kirk A. Evaluating T Cell Repopulation Post Alemtuzumab Induction with a Belatacept-Based Regimen. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Bendersky V, Xu H, Kirk A. Evaluating T Cell Repopulation Post Alemtuzumab Induction with a Belatacept-Based Regimen. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/evaluating-t-cell-repopulation-post-alemtuzumab-induction-with-a-belatacept-based-regimen/. Accessed December 12, 2024.« Back to 2017 American Transplant Congress