title: Patient HLA-DP-specific CD4+ T cells from HLA-DPB1-mismatched donor lymphocyte infusion can induce graft-versus-leukemia reactivity in the presence or absence of graft-versus-host disease.
abstract: Clinical studies have demonstrated that HLA-DPB1-mismatched allogeneic stem cell transplantation (allo-SCT) is associated with a decreased risk of disease relapse and an increased risk of graft-versus-host disease (GVHD) compared with HLA-DPB1-matched SCT. In T cell-depleted allo-SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, but a significant decreased risk of disease relapse was still observed. To investigate whether patient HLA-DP-specific CD4(+) T cell responses were frequently induced after T cell-depleted HLA-DPB1-mismatched allo-SCT and donor lymphocyte infusion (DLI), we developed a method to screen for the presence of HLA-DP-specific CD4(+) T cells using CD137 as an activation marker and analyzed 24 patient-donor combinations. The patients suffered from various B cell malignancies, multiple myeloma, and myeloid leukemias. Patient HLA-DP-specific CD4(+) T cells were detected after DLI in 13 of 18 patients who exhibited a clinical response to DLI, compared with only 1 of 6 patients without a clinical response to DLI. Eight patients developed significant GVHD. These data show that patient HLA-DP-specific CD4(+) T cells frequently occur after HLA-DPB1-mismatched T cell-depleted allo-SCT and DLI, and are associated with graft-versus-leukemia reactivity both in the presence and absence of GVHD.
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands. c.e.rutten@lumc.nl
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Rutten
authors.forename: Simone A P
authors.initials: SA
authors.lastname: van Luxemburg-Heijs
authors.forename: Constantijn J M
authors.initials: CJ
authors.lastname: Halkes
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: van Bergen
authors.forename: Erik W A
authors.initials: EW
authors.lastname: Marijt
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: Marieke
authors.initials: M
authors.lastname: Griffioen
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D059868:HLA-DP beta-Chains / Q000097:blood / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy; D006801:Humans; D008297:Male; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000097:blood / Q000276:immunology; D061349:Unrelated Donors
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9