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Infusion of clinical‐grade enriched regulatory T cells delays experimental xenogeneic graft‐versus‐host disease
Author(s) -
Han Muriel,
Lechanteur Chantal,
Lucas Sophie,
Somja Joan,
Seidel Laurence,
Belle Ludovic,
Bruck France,
Baudoux Etienne,
Giet Olivier,
Chantillon AnneMarie,
Delvenne Philippe,
Drion Pierre,
Beguin Yves,
HumbletBaron Stéphanie,
Baron Frédéric
Publication year - 2014
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12279
Subject(s) - apheresis , graft versus host disease , peripheral blood mononuclear cell , immunology , medicine , population , transplantation , andrology , chemistry , platelet , in vitro , environmental health , biochemistry
Background We investigated the ability of clinical‐grade enriched human regulatory T cells ( T reg) to attenuate experimental xenogeneic graft‐versus‐host disease ( GVHD ) induced by peripheral blood mononuclear cells ( PBMNCs ; autologous to T reg) infusion in NSG mice, as well as verified their inability to induce xenogeneic GVHD when infused alone. Study Design and Methods Human T reg were isolated from peripheral blood apheresis products with a cell separation system ( CliniMACS , M iltenyi B iotec GmbH ) using a two‐step procedure (simultaneous CD 8 and CD 19 depletion followed by CD 25‐positive selection) in six independent experiments with six different healthy volunteer donors. Sublethally (2.5 G y) irradiated NSG mice were given 2 × 10 6 cytapheresis ( PBMNC ) product cells intravenously ( IV ) without ( PBMNC group) or with 1 × 10 6 T reg ( PBMNC + T reg group), while other NSG mice received 2 × 10 6 enriched T reg alone (also in IV ; T reg group). Results The first five procedures were successful at obtaining a relatively pure T reg population (defined as >50%), while the sixth procedure, due to a technical problem, was not ( T reg purity, 42%). T reg 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 T reg alone ( T reg group) experienced clinical signs of GVHD , while, interestingly, the CD 4+ cells found in these mice 26 days after transplantation were mainly conventional T cells (median CD 25+ F ox P 3+ cells among human CD 4+ 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.