Single-cell mass cytometry maps the evolution of immune cell signatures predictive of acute graft-versus-host disease

Abstract

Allogeneic haematopoietic stem-cell transplantation (AHST) can cure patients with many diseases, but harmful acute graft-versus-host disease (aGvHD) remains a challenge. Many immune cells are implicated in the pathogenesis and control of alloreactive T-cell responses causing aGvHD, but the functionally dominant cells at different times remain unknown. Using mass cytometry to simultaneously assess alloreactive and immunoregulatory cell populations after AHST, we identified a robust early immune signature predictive of aGvHD rich in CD4 effector memory T-cells and deficient in functionally allosuppressive NK cells. Additionally, network analysis identified a heterogeneous immunoregulatory cell group (IRCG) that more accurately predicted aGVHD than any individual cell populations or established serum biomarkers. Immune signatures preceding aGvHD evolved over time, with qualitative and quantitative changes in both the alloreactive T-cell compartment and the constituent components of the IRCG. In mapping how alloreactive and immunoregulatory cell populations evolve temporally, we provide mechanistic insight into dynamic control of alloreactivity supporting development of time-sensitive targeted strategies to reduce aGvHD. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=184 HEIGHT=200 SRC="FIGDIR/small/640331v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@12bb519org.highwire.dtl.DTLVardef@7e9dbcorg.highwire.dtl.DTLVardef@a5b041org.highwire.dtl.DTLVardef@1d69a82_HPS_FORMAT_FIGEXP M_FIG C_FIG