Glycolytic metabolism of pathogenic T cells enables early detection of GVHD by 13C-MRI.

Abstract:

:Graft-versus-host disease (GVHD) is a prominent barrier to allogeneic hematopoietic stem cell transplantation (AHSCT). Definitive diagnosis of GVHD is invasive, and biopsies of involved tissues pose a high risk of bleeding and infection. T cells are central to GVHD pathogenesis, and our previous studies in a chronic GVHD mouse model showed that alloreactive CD4+ T cells traffic to the target organs ahead of overt symptoms. Because increased glycolysis is an early feature of T-cell activation, we hypothesized that in vivo metabolic imaging of glycolysis would allow noninvasive detection of liver GVHD as activated CD4+ T cells traffic into the organ. Indeed, hyperpolarized 13C-pyruvate magnetic resonance imaging detected high rates of conversion of pyruvate to lactate in the liver ahead of animals becoming symptomatic, but not during subsequent overt chronic GVHD. Concomitantly, CD4+ T effector memory cells, the predominant pathogenic CD4+ T-cell subset, were confirmed to be highly glycolytic by transcriptomic, protein, metabolite, and ex vivo metabolic activity analyses. Preliminary data from single-cell sequencing of circulating T cells in patients undergoing AHSCT also suggested that increased glycolysis may be a feature of incipient acute GVHD. Metabolic imaging is being increasingly used in the clinic and may be useful in the post-AHSCT setting for noninvasive early detection of GVHD.

journal_name

Blood

journal_title

Blood

authors

Assmann JC,Farthing DE,Saito K,Maglakelidze N,Oliver B,Warrick KA,Sourbier C,Ricketts CJ,Meyer TJ,Pavletic SZ,Linehan WM,Krishna MC,Gress RE,Buxbaum NP

doi

10.1182/blood.2020005770

subject

Has Abstract

pub_date

2021-01-07 00:00:00

pages

126-137

issue

1

eissn

0006-4971

issn

1528-0020

pii

461788

journal_volume

137

pub_type

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