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Infusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft-versus-host disease.

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Hannon, Muriel Lechanteur, Chantal Lucas, Sophie [UCL] Somja, Joan Seidel, Laurence Baron, Frédéric

BACKGROUND: We investigated the ability of clinical-grade enriched human regulatory T cells (Treg) to attenuate experimental xenogeneic graft-versus-host disease (GVHD) induced by peripheral blood mononuclear cells (PBMNCs; autologous to Treg) infusion in NSG mice, as well as verified their inability to induce xenogeneic GVHD when infused alone. STUDY DESIGN AND METHODS: Human Treg were isolated from peripheral blood apheresis products with a cell separation system (CliniMACS, Miltenyi Biotec GmbH) using a two-step procedure (simultaneous CD8 and CD19 depletion followed by CD25-positive selection) in six independent experiments with six different healthy volunteer donors. Sublethally (2.5 Gy) irradiated NSG mice were given 2 × 10(6) cytapheresis (PBMNC) product cells intravenously (IV) without (PBMNC group) or with 1 × 10(6) Treg (PBMNC + Treg group), while other NSG mice received 2 × 10(6) enriched Treg alone (also in IV; Treg group). RESULTS: The first five procedures were successful at obtaining a relatively pure Treg population (defined as >50%), while the sixth procedure, due to a technical problem, was not (Treg purity, 42%). Treg cotransfusion significantly delayed death from xenogeneic GVHD in the first five experiments, (p < 0.0001) but not in the sixth experiment. Importantly, none of the mice given enriched Treg alone (Treg group) experienced clinical signs of GVHD, while, interestingly, the CD4+ cells found in these mice 26 days after transplantation were mainly conventional T cells (median CD25+FoxP3+ cells among human CD4+ total cells were only 2.1, 3.1, and 12.2% in spleen, marrow, and blood, respectively). CONCLUSIONS: Infusion of clinical-grade enriched Treg delayed the occurrence of xenogeneic GVHD without inducing toxicity in this murine model.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2013
Language Anglais
Journal information "Transfusion" - Vol. 54, no. 2, p. 353-363 (2014)
Peer reviewed yes
e-issn 1537-2995
Publication status Publié
Affiliation UCL - SSS/DDUV - Institut de Duve
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Bibliographic reference Hannon, Muriel ; Lechanteur, Chantal ; Lucas, Sophie ; Somja, Joan ; Seidel, Laurence ; et. al. Infusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft-versus-host disease.. In: Transfusion, Vol. 54, no. 2, p. 353-363 (2014)
Permanent URL http://hdl.handle.net/2078.1/136451