Allogeneic haematopoietic cell transplantation promotes atherosclerosis in mice via CD8+ T cells
Year: 2025
Type: article
Abstract: AIMS: Patients undergoing allogeneic haematopoietic cell transplantation (allo-HCT) are at a risk of developing graft-vs.-host disease (GvHD) and are afflicted with an increased incidence of cardiovascular events. Whether allo-HCT contributes to atherosclerosis progression has not been addressed experimentally. METHODS AND RESULTS: Here, we applied a novel minor histocompatibility antigen mismatch allo-HCT mouse model by transplanting C57BL/6 mice deficient for the LDL receptor (B6.Ldlr-/-) with bone marrow (BM) or BM and T cells (BMT) from BALB/b donors (BALB/b, H-2b → B6.Ldlr-/-, and H-2b), and feeding recipients a western diet. Mild clinical GvHD symptoms ensued with low disease activity in typical GvHD target organs. However, allogeneic BMT recipients developed increased atherosclerotic lesions compared with mice receiving BM only or syngeneic BMT recipients. Atherosclerotic lesions showed a heightened infiltration of effector CD8+ T cells in the aorta of BMT recipients. Furthermore, BMT recipients exhibited significantly higher serum cholesterol levels than BM-recipients. Notably, CD8+ T-cell depletion in B6.Ldlr-/- BMT recipients reduced atherosclerotic lesion formation and decreased cholesterol levels. CONCLUSION: These data may provide a novel mechanistic underpinning for the clinically observed increased incidence of cardiovascular disease in long-term allo-HCT survivors. Moreover, we have identified CD8+ T cells as potential targets for mitigating GvHD-induced atherosclerosis.
Source: Cardiovascular Research
DOI: 10.1093/cvr/cvaf229
Authors: Ivana Jorgacevic, Haroon Shaikh, Hla Ali, Maja Bundalo, Sarah Schäfer, Michael A G Kern, Maike Büttner-Herold, Simone Reu-Hofer, Clément Cochain, Hendrik Bartolomaeus, Antoine-Emmanuel Saliba, Melanie Rösch, Giuseppe Rizzo, Estibaliz Arellano Viera, Juan Gamboa Vargas, Friederike Berberich-Siebelt, Wolfgang Herr, Louis Boon, Andreas Rosenwald, Elke Butt, Heike M Hermanns, Andreas Beilhack, Alma Zernecke
Institutions: Universitätsklinikum Würzburg, University of Würzburg, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Inserm, Université Paris Cité, Paris Cardiovascular Research Center, Helmholtz Centre for Infection Research, Helmholtz Institute for RNA-based Infection Research, University Hospital Regensburg, Państwowa Wyższa Szkoła Zawodowa we Włocławku, Comprehensive Cancer Center Mainfranken
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,329
Funder: Deutsche Forschungsgemeinschaft
OpenAlex ID: W4416411675