title: Generation of cytotoxic donor CD8+ T cells against relapsing leukemic cells following allogeneic transplantation by stimulation with leukemic cell- or leukemic lysate pulsed donor cell-derived dendritic cells.
abstract: To treat leukemia relapse after allogeneic hematopoietic stem cell transplantation (HSCT), we investigated the possibility of immunotherapy using donor CD8+ T cells that were generated by stimulating leukemic cell-derived dendritic cells (leukemic-DCs) or leukemic cell lysate pulsed donor cell-derived DCs (donor-DCs). Leukemic- and donor-DCs were generated from mononuclear cells of patients and CD14+ cells of HLA-matched donors, respectively. The expression of CD80, CD83, CD86, CD1a, and CD40 on leukemic-DCs was significantly lower than that on donor-DCs. Donor-DCs exhibited a higher capacity to stimulate allogeneic T cells compared with leukemic-DCs. Donor CD8+ T cells stimulated by leukemic- or donor-DCs were more cytotoxic than unprimed CD8+ T cells, and slightly higher cytotoxicity was observed with donor-DCs compared to leukemic-DCs. This study indicates that leukemic- or donor-DCs pulsed with leukemic cell lysates can effectively prime donor cytotoxic T cells in vitro, and that they may be used as a potential alternative tool for treating leukemic patients who relapse after allogeneic HSCT.
authors.affiliation: Genome Research Center for Hematopoietic Diseases, Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Chan-Eun
authors.initials: CE
authors.lastname: Nam
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Nam
authors.forename: Hyun-Chul
authors.initials: HC
authors.lastname: Lee
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
authors.forename: Myong-Suk
authors.initials: MS
authors.lastname: Park
authors.forename: Bo-Hwa
authors.initials: BH
authors.lastname: Choi
authors.forename: Won-Hyun
authors.initials: WH
authors.lastname: Song
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Lee
authors.forename: Kyeong-Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Hoon
authors.initials: H
authors.lastname: Kook
authors.forename: Tai-Ju
authors.initials: TJ
authors.lastname: Hwang
authors.forename: Masao
authors.initials: M
authors.lastname: Takei
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006086:Graft vs Host Disease / Q000209:etiology; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D012008:Recurrence; D014184:Transplantation, Homologous