Reduced mitochondrial respiration in peripheral T cells after paediatric heamatopoietic stem cell transplantation
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Reduced mitochondrial respiration in peripheral T cells after paediatric heamatopoietic stem cell transplantation. / Mølgaard, Kasper; Kielsen, Katrine; Ifversen, Marianne; Met, Özcan; Svane, Inge Marie; Müller, Klaus.
In: Frontiers in Immunology, Vol. 14, 1327977, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Reduced mitochondrial respiration in peripheral T cells after paediatric heamatopoietic stem cell transplantation
AU - Mølgaard, Kasper
AU - Kielsen, Katrine
AU - Ifversen, Marianne
AU - Met, Özcan
AU - Svane, Inge Marie
AU - Müller, Klaus
N1 - Publisher Copyright: Copyright © 2024 Mølgaard, Kielsen, Ifversen, Met, Svane and Müller.
PY - 2024
Y1 - 2024
N2 - Background: 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: 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: 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: 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.
AB - Background: 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: 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: 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: 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.
KW - acute graft-versus-host disease
KW - hematopoietic stem cell transplantation
KW - mitochondrial fitness
KW - real-time metabolism
KW - spare respiratory capacity
KW - T cells
U2 - 10.3389/fimmu.2023.1327977
DO - 10.3389/fimmu.2023.1327977
M3 - Journal article
C2 - 38268913
AN - SCOPUS:85182806558
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 1327977
ER -
ID: 388331438