Treg suppression mechanisms of acute GVHD

Lohmeyer JK, Hirai T, Turkoz M, et al. Analysis of T Cell Repertoire and Transcriptome Identifies Mechanisms of Regulatory T Cell (Treg) Suppression of GVHD. Blood. 2022; (doi: 10.1182/blood.2022017982).

Researchers have learned more about the role of regulatory T cells (Treg) in combating graft-versus-host disease (GVHD). While they recognize that Treg can protect against this complication of hematopoietic cell transplantation while maintaining the graft-versus-tumor (GVT) activity the procedure affords, the mechanisms supporting this function until now have been a mystery. Recent explorations involving transcriptomic analysis and paired T cell receptor repertoire sequencing provide new understanding. Scientists now know that Treg are activated and experience clonal expansion during in vivo suppression of acute GVHD. At the same time, Treg modulated conventional T cells' (Tcon) transciptome, primarily CD4 Tcon but also CD8 Tcon, through several non-redundant pathways. Although activation of alloreactive Tcon clones persisted throughout this process, their expansion was stunted to a meaningful extent. Importantly, Treg did not derail the induction of gene sets that contribute to the GVT effect. The findings will help transition the immunotherapy intervention of CD4+FOXP3+Treg to clinical practice.

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Tags: patient care, GVHD, Cellular therapy, Graft versus host disease, Acute GVHD, aGVHD, cell therapy, graft-versus-host disease, graft-vs-host disease, T cells, T cell