Dudreuilh C, Basu S, Shaw O, Burton H, Mamode N, Harris F, Tree T, Nedyalko P, Terranova-Barberio M, Lombardi G, Scottà C, Dorling A
Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.
Centre for Nephrology, Urology and Transplantation, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.
Front Transplant. 2023 Oct 30;2:1165320. doi: 10.3389/frtra.2023.1165320. eCollection 2023.
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.
We recruited prospectively healthy volunteers (HV) ( = 9), non-sensitised patients on haemodialysis (HD) ( = 9) and HS individuals, all of whom were on haemodialysis ( = 15).
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).
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.
高度致敏（HS）患者占肾移植等待名单上患者的30%。当他们接受移植时，有急性/慢性排斥反应和长期移植物丢失的高风险。调节性T细胞（Tregs，CD4CD25CD127）是参与抑制免疫同种异体反应的细胞。一个特殊的亚群，称为滤泡调节性T细胞（Tfr，CXCR5Bcl-6），参与调节生发中心内效应T细胞与B细胞之间的相互作用，并且可以在外周血中发现。因此，我们想要鉴定HS个体外周血中Tregs的特定亚群。
我们前瞻性招募了健康志愿者（HV）（n = 9）、接受血液透析（HD）的未致敏患者（n = 9）和均接受血液透析的HS个体（n = 15）。
我们比较了HV、HD和HS的Treg表型。与HV相比，HS患者有更多的CD161 Tregs（P = 0.02）和更多的CD45RACCR7效应T细胞（Teffs）（P = 0.04，能够归巢至生发中心的记忆性Teffs）。与HD患者相比，HS患者有更多的Bcl-6 Tregs（P < 0.05）、更少的Th1样Tregs、更多的Th2样Tregs（P < 0.001）和更多的CD161（P < 0.05）Tregs。该群体已被描述为具有高度抑制性。HD患者在一个Th17样CD161效应性Treg簇（簇iii.，CCR6CCR4CXCR3 CD39CD15sICOSCCR7CD161）中存在缺陷（P < 0.05）。
这是第一项展示HS患者深入Treg表型的研究。我们证实，与接受HD的未致敏患者相比，HS患者有更多来自群体III（CD4CD25CD127CD45RA）的Th17样CD161效应性Treg。在移植背景下，这种高度抑制性Tregs群体的临床相关性仍有待确定。
