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Regulatory T Cells Suppress Memory IFN-Gamma Production in Highly Sensitised Patients

C. Dudreuilh1, S. Basu1, O. Shaw2, H. Burton1, C. Domingo-Vila1, T. Tree1, G. Lombardi1, C. Scotta1, A. Dorling1

1King's College London, London, United Kingdom, 2Viapath Clinical Transplantation Laboratory, Guy's Hospital, London, United Kingdom

Meeting: 2022 American Transplant Congress

Abstract number: 1268

Keywords: Alloantigens, Highly-sensitized, Kidney transplantation, T cells

Topic: Basic Science » Basic Science » 10 - Treg/Other Regulatory Cell/Tolerance

Session Information

Session Name: Treg/Other Regulatory Cell/Tolerance

Session Type: Poster Abstract

Date: Monday, June 6, 2022

Session Time: 7:00pm-8:00pm

 Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: Highly sensitized patients (HS) present worse long-term outcome after transplantation compared to those without donor-specific antibodies (DSA). It has been suggested that desensitisation using anti-CD19 depleting agents do not have satisfying long term outcomes, as they remove B cells with a regulatory phenotype (“Bregs”). In vitro anti-donor IFNγ production correlates with progression of graft dysfunction and fewer regulatory Tcells (Tregs) in patients with chronic rejection. This project aims to understand B cells/Tregs interactions in HS patients.

*Methods: We prospectively recruited HS patients on dialysis, isolated their Tregs and expanded these cells using established protocols (Interleukin-2 + Rapamycin). IFNγ production by CD8-depleted PBMC (+/- additional depletion of CD19+ cells) in response to HLA proteins (PureProt®) was tested in Fluorospot to assess the memory immune alloresponse at baseline and when Tregs were added.

*Results: Out of 16 patients recruited, 10/16 patients (63%) had a background of transplantation with a nephrectomy in 4/10 and 4/10 (25%) were still receiving immunosuppressive drugs. We managed to expand Tregs from 11 patients (Table 1). Three patients had IFNγ production in CD8-depleted PBMCs challenged with an HLA protein they had been sensitised to (HLA Specific Reactivity group = “HLA SR”). Autologous ex vivo expanded Tregs regulated IFNγ production in 1/3 patients (Figure 1A). When CD19- were depleted, 5/10 patients presented an increase of IFNγ production (4 of those with no response from CD8-depleted PBMC) (Figure 1B). Interestingly, autologous ex vivo expanded Tregs managed to regulate IFNγ production in 5/5 (100%) of these patients.

*Conclusions: Autologous ex vivo expanded Tregs are able to regulate IFNγ production in HS patients when the B cells are depleted, but not when the B cells are present. This demonstrates complex interactions between B cells, Tregs and Teffectors. The determinants of these molecular relationships are currently under investigation.

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To cite this abstract in AMA style:

Dudreuilh C, Basu S, Shaw O, Burton H, Domingo-Vila C, Tree T, Lombardi G, Scotta C, Dorling A. Regulatory T Cells Suppress Memory IFN-Gamma Production in Highly Sensitised Patients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/regulatory-t-cells-suppress-memory-ifn-gamma-production-in-highly-sensitised-patients/. Accessed May 28, 2025.

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