Scientists have investigated the mechanisms behind the restoration of the T cell subsets after a stem cell transplant.
Dr Georg Stary of MedUni Vienna, Austria, and colleagues set out to understand the causes of complications, and ways to improve the success of stem cell transplants. “The success of haematopoietic stem cell transplantation is threatened by complications including leukaemia relapse or graft-versus-host-disease,” they write in the journal Clinical Immunology.
To investigate the underlying processes of T cell recovery, the team analysed skin and blood T cells donated by patients at various time points before and after a stem cell transplant. They found rapid recovery of effector T cells, with specific enzymes called histone deacetylases (HDACs) being essential for this process, but slower regrowth of “protective” regulatory T cells.
In further tests, they found that inhibiting different classes of HDACs after transplant could control the balance of T cell regrowth. “Epigenetic and gene-regulatory programmes diverged greatly between skin and blood T cells,” they write.
Dr Stary said: “With the potential of HDAC inhibitors to modulate T cells after stem cell transplantation, we have discovered an innovative approach to influence the epigenetics of T cells at specific time points after stem cell transplantation and to increase the safety of the therapy.
“Our study underlines the importance of epigenetic regulators in restoring the immune system and shows new therapeutic possibilities for achieving T-cell balance after stem cell transplantation."
Pandey RV, Strobl J, Redl A, Unterluggauer L, Gail L, Kleissl L, Müller S, Atzmüller D, Fife-Gernedl V, Krausgruber T, Knaus H, Mitterbauer M, Wohlfarth P, Rabitsch W, Bock C, Stary G. (2023) “Epigenetic regulation of T cell lineages in skin and blood following hematopoietic stem cell transplantation.” Clinical Immunology, doi: 10.1016/j.clim.2023.109245
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