T Cell and Cytokine Dynamics in the Blood of Patients after Hematopoietic Stem Cell Transplantation and Multipotent Mesenchymal Stromal Cell Administration

•The administration of mesenchymal stromal cells (MSCs) exerts a positive effect on restoration of T cell subpopulations and recovery of immune system of patients after allogeneic hematopoietic stem cell transplantation.•Three days after MSC injection, the numbers of CD8+ effector cells (CD8+TE, CD8...

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Published in:Transplantation and cellular therapy 2023-02, Vol.29 (2), p.109.e1-109.e10
Main Authors: Petinati, Nataliya, Davydova, Yulia, Nikiforova, Ksenia, Bigildeev, Alexey, Belyavsky, Alexander, Arapidi, Georgiy, Drize, Nina, Kuzmina, Larisa, Parovichnikova, Elena, Savchenko, Valeriy
Format: Article
Language:English
Subjects:
Allogeneic hematopoietic stem cells transplantation
CD4-Positive T-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - pathology
Cytokines
Cytokines - metabolism
Graft vs Host Disease - prevention & control
Growth factors
Hematopoietic Stem Cell Transplantation
Humans
Memory T cell subpopulations
Mesenchymal Stem Cells - metabolism
Multipotent mesenchymal stromal cells
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Summary:•The administration of mesenchymal stromal cells (MSCs) exerts a positive effect on restoration of T cell subpopulations and recovery of immune system of patients after allogeneic hematopoietic stem cell transplantation.•Three days after MSC injection, the numbers of CD8+ effector cells (CD8+TE, CD8+TM, and CD8+EM) increased significantly.•Faster recovery of the CD4+ cell population was observed in patients at 30 days after MSC infusion compared to patients without MSC infusion.•The concentrations of proinflammatory and anti-inflammatory cytokines IL-6, IL-8, IL-17, TNF-α, and IFN-γ, were increased significantly in patients injected with MSCs. Multipotent mesenchymal stromal cells (MSCs) are currently under intensive investigation for the treatment and prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), owing to their substantial immunomodulatory properties. The responses of recipients to MSC infusion following allo-HSCT are not yet well understood. T cells are central to the adaptive immune system, protecting the organism from infection and malignant cells. Memory T cells with different phenotypes, gene expression profiles, and functional properties are critical for immune processes regulation. The aim of this study was to study the dynamics of memory T cell subpopulations and cytokines in the blood of allo-HSCT recipients after MSC administration. In clinical trial NCT01941394, patients after allo-HSCT were randomized into 2 groups, one receiving standard GVHD prophylaxis and the other also receiving MSC infusion on the day of leukocyte recovery to 1000 cells/μL (engraftment, day E0). Blood samples of patients from both groups were analyzed on days E0, E+3, and E+30. T cell subpopulations were studied by flow cytometry, and cytokine concentrations were evaluated by the Bio-Plex Pro Human Cytokine Panel. Administration of MSCs to patients on day E0 did not affect the overall dynamics of restoration of absolute numbers and proportions of T and B lymphocytes after 3 and 30 days. At 3 days after MSC injection, only the numbers of CD8+ effector cells (CD8+TE, CD8+TM, and CD8+EM) were found to increase significantly. A significant increase in the number of CD4+ cells after 30 days compared to day E0 was observed only in patients who received MSCs, indicating faster recovery of the CD4+ cell population following MSC injection. An increase in CD8+ cell number by day E+30 was significant regardless
ISSN:2666-6367
2666-6367
DOI:10.1016/j.jtct.2022.10.030