Ex vivo-expanded CD4+CD25+ immunoregulatory T cells prevent graft-versus-host-disease by inhibiting activation/differentiation of pathogenic T cells.
CD4+CD25+ immunoregulatory T cells (Tregs) can be administered to inhibit graft-vs-host disease (GVHD) while preserving graft-vs-leukemia activity after allogeneic bone marrow transplantation in mice. Preclinical studies suggest that it is necessary to infuse as many Tregs as conventional donor T cells to achieve a clinical effect on GVHD. Thus, it would be necessary to expand Tregs ex vivo before transplantation. Two strategies have been proposed: expansion of Tregs stimulated by anti-CD3/CD28-coated microbeads for polyclonal activation or by host-type allogeneic APCs for selecting Tregs specific for host Ags. In this study, we describe the mechanisms by which ex vivo-expanded Tregs act on donor T cells to prevent GVHD in mice. We demonstrate that expanded Tregs strongly inhibited the division, expansion, and differentiation of donor T cells, with a more pronounced effect with Tregs specific for host Ags. These latter cells permit the efficient and durable control of GVHD and favor immune reconstitution.
Trenado
Aurélie
A
Biologie et Thérapeutique des Pathologies Immunitaires, Hôpital Pitié-Salpêtrière, Paris, France.
Sudres
Muriel
M
Tang
Qizhi
Q
Maury
Sébastien
S
Charlotte
Frédéric
F
Grégoire
Sylvie
S
Bonyhadi
Mark
M
Klatzmann
David
D
Salomon
Benoît L
BL
Cohen
José L
JL
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014019:Tissue Donors