It is now well-established that regulatory T cells (Treg) represent a heterogeneous group of CD4+ T cells. Previous studies have demonstrated that Treg homeostasis was impacted by allogeneic hematopoietic cell transplantation (allo-HCT) and particularly so in patients with chronic graft-versus-host disease (GVHD). Here, we first assessed the ability of various Treg subsets to phosphorylate STAT5 in response to IL-2 or IL-7 stimulation in vitro. We then compared the frequencies of different Treg subtypes in healthy controls as well as in allo-HCT patients with or without chronic GVHD. The highest phosphorylated STAT5 (pSTAT5) signal in response to IL-2 was observed in the CD45RO+CD26−CD39+HLA-DR+ Treg fraction. In contrast, naive Treg were mostly less susceptible to IL-2 stimulation in vitro. Following IL-7 stimulation, most Treg subpopulations upregulated pSTAT5 expression but to a lesser extent than conventional T cells. Compared to healthy controls, allo-HCT patients had lower frequencies of the naive CD45RAbrightCD26+ Treg subpopulation but higher frequencies of the most differentiated memory CD45RO+CD26−CD39+ Treg subpopulations. Further, unbiased analysis revealed that six Treg clusters characterized by high expression of CD25, HLA-DR, and ICOS were significantly more frequent in patients with no or with limited chronic GVHD than in those with moderate/severe chronic GVHD.
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This study was supported in part by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No. 643776 (TREGeneration), by the Foundation contre le Cancer (FBC), Belgium, FBC # FAF-C/2016/889 Grant and the National Fund for Scientific Research (FNRS), Belgium, research Grant PDR T006915F and PDR T.0016.20.CR is Televie PhD student and FB is Senior Research Associate at the FNRS, Belgium.
Conflict of interest
FB has received travel grants and/or speaker honoraria from Celgene, AbbVie, Novartis, Pfizer, and Sanofi. The other authors declare that they have no conflict of interest.
The study was approved by the Ethics Committee of the CHU of Liège (protocol number TJB1609). All volunteers and patients provided their written informed consent.
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Ritacco, C., Ehx, G., Grégoire, C. et al. High proportion of terminally differentiated regulatory T cells after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant (2021). https://doi.org/10.1038/s41409-021-01221-0