Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion.
Fiche publication
Date publication
janvier 2006
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BITTARD Hugues, Pr CHALOPIN Jean-Marc, Pr DE CARVALHO BITTENCOURT Marcelo, Dr FERRAND Christophe, Pr SEILLES Estelle, Dr PERRUCHE Sylvain
Tous les auteurs :
Kleinclauss F, Perruche S, Masson E, de Carvalho Bittencourt M, Biichle S, Remy-Martin JP, Ferrand C, Martin M, Bittard H, Chalopin JM, Seilles E, Tiberghien P, Saas P
Lien Pubmed
Résumé
Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.
Référence
Cell Death Differ. 2006 Jan;13(1):41-52.