Multimodal immune cell phenotyping in GI biopsies reveals microbiome-related T cell modulations in human GvHD.

Acute graft-versus-host disease (aGvHD) is a significant complication after allogeneic hematopoietic stem cell transplantation (aHSCT), but major factors determining disease severity are not well defined yet. By combining multiplexed tissue imaging and single-cell RNA sequencing on gastrointestinal biopsies from aHSCT-treated individuals with fecal microbiome analysis, we link high microbiome diversity and the abundance of short-chain fatty acid-producing bacteria to the sustenance of suppressive regulatory T cells (Tregs). Furthermore, aGvHD severity strongly associates with the clonal expansion of mainly CD8 T cells, which we find distributed over anatomically distant regions of the gut, persistent over time, and inversely correlated with the presence of suppressive Tregs. Overall, our study highlights the pathophysiological importance of expanded CD8 T cell clones in the progression of aGvHD toward more severe clinical manifestations and strongly supports the further development of microbiome interventions as GvHD treatment via repopulation of the gut Treg niche to suppress inflammation.
Competing Interests: Declaration of interests D.H.B. is a co-founder of STAGE Cell Therapeutics GmbH (now Juno Therapeutics/Bristol Myers Squibb) and T Cell Factory B.V. (now Kite/Gilead). D.H.B. has a consulting contract with and receives sponsored research support from Juno Therapeutics/BMS. H.P. is a consultant for Gilead, AbbVie, Pfizer, Novartis, Neovii, Janssen-Cilag, Servier, and Bristol Myers Squibb. H.P. has received research funding from Bristol Myers Squibb. E.H. is a consultant of Maat Pharma, PharmaBiome, Novartis, Neovii, and Medac.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)