Highly sensitised individuals present a distinct Tregs signature compared to unsensitised individuals on hemodialysis

TY - JOUR

T1 - Highly sensitised individuals present a distinct Tregs signature compared to unsensitised individuals on hemodialysis

AU - Dudreuilh, Caroline

AU - Basu, Sumoyee

AU - Shaw, Olivia

AU - Burton, Hannah

AU - Mamode, Nizam

AU - Petrov, Nedyalko

AU - Barberio, M. Terranova

AU - Lombardi, Giovanna

AU - Scotta, Cristiano

AU - Dorling, Anthony

PY - 2023/2

Y1 - 2023/2

N2 - 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) (CD4+CD25hiCD127lo) are T cells involved in suppression of immune alloresponses. A particular subset, called T follicular regulatory T cells (Tfr, CXCR5+Bcl-6+) is involved in regulating T effectors and B cells interactions within the germinal centre. We wanted to assess if we could identify specific subsets of Tregs in highly sensitised individuals.We recruited prospectively healthy volunteers (HV) (n=9), non-sensitised patients on hemodialysis (HD) (n=9) and highly sensitised (HS) individuals on dialysis (n=15). We compared the Tregs phenotypes of HV, HD and HS. HS patients had more CD161+ Tregs (p=0.02), more CD45RA-CCR7- Teffs (p=0.04, memory Teffs able to home to the germinal centre) and more PD-1+ Teffs compared to HV. They had more Bcl-6+ Tregs (pThis is the first study presenting a deep Tregs phenotype in highly sensitised patients. We confirmed that HS patients had more of a Th17-like CD161+ effector Tregs from population III (CD4+CD25hiCD127loCD45RA-) (cluster iii) compared to unsensitised HD.

AB - 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) (CD4+CD25hiCD127lo) are T cells involved in suppression of immune alloresponses. A particular subset, called T follicular regulatory T cells (Tfr, CXCR5+Bcl-6+) is involved in regulating T effectors and B cells interactions within the germinal centre. We wanted to assess if we could identify specific subsets of Tregs in highly sensitised individuals.We recruited prospectively healthy volunteers (HV) (n=9), non-sensitised patients on hemodialysis (HD) (n=9) and highly sensitised (HS) individuals on dialysis (n=15). We compared the Tregs phenotypes of HV, HD and HS. HS patients had more CD161+ Tregs (p=0.02), more CD45RA-CCR7- Teffs (p=0.04, memory Teffs able to home to the germinal centre) and more PD-1+ Teffs compared to HV. They had more Bcl-6+ Tregs (pThis is the first study presenting a deep Tregs phenotype in highly sensitised patients. We confirmed that HS patients had more of a Th17-like CD161+ effector Tregs from population III (CD4+CD25hiCD127loCD45RA-) (cluster iii) compared to unsensitised HD.

M3 - Article

JO - Frontiers

JF - Frontiers

ER -