AUTHOR=Mølgaard Kasper , Kielsen Katrine , Ifversen Marianne , Met Özcan , Svane Inge Marie , Müller Klaus TITLE=Reduced mitochondrial respiration in peripheral T cells after paediatric heamatopoietic stem cell transplantation JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1327977 DOI=10.3389/fimmu.2023.1327977 ISSN=1664-3224 ABSTRACT=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.