High proportion of terminally differentiated regulatory T cells after allogeneic hematopoietic stem cell transplantation
- 4 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Bone Marrow Transplantation
- Vol. 56 (8), 1828-1841
- https://doi.org/10.1038/s41409-021-01221-0
Abstract
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.Funding Information
- EC | Horizon 2020 Framework Programme (643776)
- Stichting Tegen Kanker (FBC # FAF-C/2016/889)
- Fonds De La Recherche Scientifique - FNRS (PDR T.0016.20.CR)
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