Reduced mitochondrial respiration in peripheral T cells after paediatric heamatopoietic stem cell transplantation.

T cells acute graft-versus-host disease hematopoietic stem cell transplantation mitochondrial fitness real-time metabolism spare respiratory capacity

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 25 10 2023
accepted: 15 12 2023
medline: 25 1 2024
pubmed: 25 1 2024
entrez: 25 1 2024
Statut: epublish

Résumé

Recovery and functional differentiation of T-cell subsets are central for the development of immune function and complications after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about the cellular respiration and factors influencing T-cell metabolic fitness during immune maturation after HSCT. We included 20 HSCT patients and analysed mitochondrial oxidative phosphorylation and mitochondrial fitness in peripheral blood mononuclear cell samples collected at days +90 and +180 after HSCT. Phenotypic analysis revealed lower overall T-cell counts, lower CD4+/CD8+ ratio and a skewed distribution of early T-cell subsets at day +90, gradually recovering by day +180. Although ATP turnover in HSCT patients was similar to healthy controls, the spare respiratory capacity (SRC) of T cells, reflecting the available energy reserve, was significantly reduced at day +90 and +180 compared to healthy controls. This reduction in SRC was not correlated with the occurrence of acute graft-versus-host disease (aGVHD), the intensity of conditioning regimens and markers of T-cell exhaustion. We found significantly depressed SRC until six months post-HSCT, but we were not able to identify transplant-related risk factors or associations with the clinical outcome.

Sections du résumé

Background UNASSIGNED
Recovery and functional differentiation of T-cell subsets are central for the development of immune function and complications after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about the cellular respiration and factors influencing T-cell metabolic fitness during immune maturation after HSCT.
Method UNASSIGNED
We included 20 HSCT patients and analysed mitochondrial oxidative phosphorylation and mitochondrial fitness in peripheral blood mononuclear cell samples collected at days +90 and +180 after HSCT.
Results UNASSIGNED
Phenotypic analysis revealed lower overall T-cell counts, lower CD4+/CD8+ ratio and a skewed distribution of early T-cell subsets at day +90, gradually recovering by day +180. Although ATP turnover in HSCT patients was similar to healthy controls, the spare respiratory capacity (SRC) of T cells, reflecting the available energy reserve, was significantly reduced at day +90 and +180 compared to healthy controls. This reduction in SRC was not correlated with the occurrence of acute graft-versus-host disease (aGVHD), the intensity of conditioning regimens and markers of T-cell exhaustion.
Conclusion UNASSIGNED
We found significantly depressed SRC until six months post-HSCT, but we were not able to identify transplant-related risk factors or associations with the clinical outcome.

Identifiants

pubmed: 38268913
doi: 10.3389/fimmu.2023.1327977
pmc: PMC10806108
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1327977

Informations de copyright

Copyright © 2024 Mølgaard, Kielsen, Ifversen, Met, Svane and Müller.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Auteurs

Kasper Mølgaard (K)

National Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Copenhagen, Denmark.

Katrine Kielsen (K)

Institute of Inflammatory Research, Rigshospitalet, Copenhagen, Denmark.

Marianne Ifversen (M)

Hematopietic Stem Cell Transplantation and Primary Immune Deficiency, Department of Paediatric and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Özcan Met (Ö)

National Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Copenhagen, Denmark.

Inge Marie Svane (IM)

National Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Copenhagen, Denmark.

Klaus Müller (K)

Institute of Inflammatory Research, Rigshospitalet, Copenhagen, Denmark.
Hematopietic Stem Cell Transplantation and Primary Immune Deficiency, Department of Paediatric and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Classifications MeSH