title: Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras.
abstract: Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs.
authors.affiliation: Transplantation Research Center, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Arnab
authors.initials: A
authors.lastname: Ghosh
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koestner
authors.forename: Martin
authors.initials: M
authors.lastname: Hapke
authors.forename: Verena
authors.initials: V
authors.lastname: Schlaphoff
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Rolf
authors.initials: R
authors.lastname: Baumann
authors.forename: Christian
authors.initials: C
authors.lastname: Koenecke
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sauer
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D007938:Leukemia / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell