[In vitro anti-leukemia activity of cord blood original cytotoxic T lymphocytes].
OBJECTIVE
Cord blood transplantation (CBT) possesses graft-versus-leukemia (GVL) effect. It is possible to cure leukemia if specific cytotoxic T lymphocytes (CTLs) can be induced from lymphocytes in cord blood (CB), and be used to eradicate minimal residual disease (MRD) in leukemia patients. This study was to induce CTLs from cord blood, and explore its in vitro anti-leukemia activity.


METHODS
Dendritic cells (DCs) were generated from 8 samples of cord blood mononuclear cells by culturing with multiple cytokines. Immature DCs were pulsed with apoptotic leukemia cells to present leukemic antigens to cord blood original lymphocytes to obtain CTLs. The characteristics of maturation of DCs were evaluated by morphology and flow cytometry. Anti-leukemia effect of CTLs was measured by lactate dehydrogenase release assay.


RESULTS
Typical DCs were induced from all of the 8 samples. Expressions of immunologic markers CD1a(+), HLA-DR(+), CD86(+), CD83(+) on DCs were significantly higher after culturing than before culturing [(29.6+/-13.8)% vs. (1.8+/-1.9)%, (81.1+/-17.8)% vs. (19.4+/-10.6)%, (42.7+/-21.9)% vs. (7.5+/-5.3)%, (8.0+/-6.9)% vs. (1.4+/-1.1)%, respectively, P< 0.05]. When E:T ratio was 50:1, CTLs showed far higher cytotoxicity to uncultured acute myeloid leukemia (AML) cells than to K562 cells, and to mononuclear cells of bone marrow from the corresponding patients in complete remission phase (CR-MNCs) [(52.6+/-21.0)% vs. (18.2+/-20.2)%, and (3.3+/-6.3)%, P < 0.05].


CONCLUSIONS
Mature DCs derived from cord blood, which loaded leukemia antigens, could induce leukemia-specific CTLs. The CTLs have vigorous cytotoxicity to original leukemia cells rather than CR-MNCs.
Zeng
Lin-Juan
LJ
Oncology and Hematology Center, The First Affiliated Hospital, Guangzhou Medical College, Guangzhou, Guangdong, 510230, P. R. China. tanhuo@public.gd.cn.
Tan
Huo
H
D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D017209:Apoptosis / Q000276:immunology; D051940:B7-2 Antigen / Q000032:analysis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018949:Antigens, CD1; D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C419393:CD1a antigen