Highly Sensitised Individuals Present a Distinct Treg Signature Compared to Unsensitised Individuals on Haemodialysis

Overview

Journal Front Transplant

Specialty General Surgery

Date 2024 Jul 12

PMID 38993845

Authors

C Dudreuilh

S Basu

O Shaw

H Burton

N Mamode

F Harris

T Tree

P Nedyalko

M Terranova-Barberio

G Lombardi

C Scotta

A Dorling

Affiliations

Soon will be listed here.

Abstract

Introduction: Highly sensitised (HS) patients represent up to 30% of patients on the kidney transplant waiting list. When they are transplanted, they have a high risk of acute/chronic rejection and long-term allograft loss. Regulatory T cells (Tregs) (CD4CD25CD127) are cells involved in the suppression of immune alloresponses. A particular subset, called T follicular regulatory T cells (Tfr, CXCR5Bcl-6), is involved in regulating interactions between T effectors and B cells within the germinal centre and can be found in peripheral blood. Therefore, we wanted to identify specific subsets of Tregs in the peripheral blood of HS individuals.

Methods: We recruited prospectively healthy volunteers (HV) ( = 9), non-sensitised patients on haemodialysis (HD) ( = 9) and HS individuals, all of whom were on haemodialysis ( = 15).

Results: We compared the Treg phenotypes of HV, HD and HS. HS patients had more CD161 Tregs ( = 0.02) and more CD45RACCR7 T effectors (Teffs) ( = 0.04, memory Teffs able to home to the germinal centre) compared to HVs. HS patients had more Bcl-6 Tregs ( < 0.05), fewer Th1-like Tregs, more Th2-like Tregs ( < 0.001) and more CD161 ( < 0.05) Tregs compared to HD patients. This population has been described to be highly suppressive. HD had a deficiency in a Th17-like CD161 effector Treg cluster (cluster iii., CCR6CCR4CXCR3 CD39CD15sICOSCCR7CD161) ( < 0.05).

Discussion: This is the first study presenting a deep Treg phenotype in HS patients. We confirmed that HS patients had more of a Th17-like CD161 effector Treg from population III (CD4CD25CD127CD45RA) compared to non-sensitised patients on HD. The clinical relevance of this highly suppressive Tregs population remains to be determined in the context of transplantation.

Citing Articles

Activation and Regulation of Indirect Alloresponses in Transplanted Patients With Donor Specific Antibodies and Chronic Rejection.

Basu S, Dudreuilh C, Shah S, Sanchez-Fueyo A, Lombardi G, Dorling A Transpl Int. 2024; 37:13196.

PMID: 39228658 PMC: 11368725. DOI: 10.3389/ti.2024.13196.

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