Publikationsdatenbank

Cyclosporine a but not corticosteroids support efficacy of ex vivo expanded, adoptively transferred human Tregs in GvHD (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Landwehr-Kenzel, Sybille

Zobel, Anne

Schmitt-Knosalla, Isabela

Forke, Anne

Hoffmann, Henrike

Schmueck-Henneresse, Michael

Klopfleisch, Robert (WE 12)

Volk, Hans-Dieter

Reinke, Petra

Quelle

Frontiers in immunology

Bandzählung: 12

Seiten: Article 716629

ISSN: 1664-3224

Sprache

Englisch

Verweise

URL (Volltext): https://www.frontiersin.org/articles/10.3389/fimmu.2021.716629/full

DOI: 10.3389/fimmu.2021.716629

Pubmed: 34707604

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Reshaping the immune balance by adoptive transfer of regulatory T-cells (Tregs) has emerged as a promising strategy to combat undesired immune reactions, including in Graft-versus-Host Disease (GvHD), which is the most lethal non-relapse complication of allogeneic hematopoietic stem cell transplantation. Currently however, little is known about the potentially inhibitory in vivo effects of conventional immunosuppressive drugs, which are routinely used to treat GvHD, on adoptively transferred Tregs. Here we demonstrate drug-specific effects of the conventional immunosuppressive drugs Cyclosporine A, Mycophenolate mofetil and methylprednisolone on adoptively transferred Tregs in a humanized NOD/SCID/IL2Rgamma-/- GvHD mouse model. The clinical course of GvHD and postmortem organ histology, including cellular organ infiltration, showed that co-administration of Cyclosporine A and Tregs is highly beneficial as it enhanced Treg accumulation at inflammatory sites like lung and liver. Similarly, co-administration of Mycophenolate mofetil and Tregs improved clinical signs of GvHD. In contrast, co-administration of methylprednisolone and Tregs resulted in reduced Treg recruitment to inflammatory sites and the fast deterioration of some animals. Consequently, when clinical trials investigating safety and efficacy of adjunctive Treg therapy in GvHD are designed, we suggest co-administering Cyclosporine A, whereas high doses of glucocorticosteroids should be avoided.