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.
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.
Lee
Je-Jung
JJ
Genome Research Center for Hematopoietic Diseases, Chonnam National University Hospital, Gwangju, South Korea.
Nam
Chan-Eun
CE
Nam
Jong-Hee
JH
Lee
Hyun-Chul
HC
Chung
Ik-Joo
IJ
Park
Myong-Suk
MS
Choi
Bo-Hwa
BH
Song
Won-Hyun
WH
Lee
Il-Kwon
IK
Park
Kyeong-Soo
KS
Kook
Hoon
H
Hwang
Tai-Ju
TJ
Takei
Masao
M
Takaue
Yoichi
Y
Kim
Hyeoung-Joon
HJ
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