Induction of autologous CD4- and CD8-mediated T-cell responses against acute lymphocytic leukemia cell line using apoptotic tumor cell-loaded dendritic cells.
OBJECTIVE
Several studies have demonstrated that dendritic cells (DCs) pulsed with tumor lysate or apoptotic tumor cells can elicit effective T-cell responses. This technique does not require the identification of the tumor antigen or HLA haplotype of the patient. We applied this approach to induce HLA class I- and class II-restricted T-cell responses directed against autologous acute lymphocytic leukemia (B-ALL) cell line NH-1.


METHODS
Autologous T cells were stimulated by apoptotic tumor cell-loaded DCs generated from a patient with ALL. The stimulated and expanded T cells were isolated into CD8(+) T-cell line and CD4(+) T-cell line, and each of them was examined as to their functions.


RESULTS
Both CD8(+) and CD4(+) T-cell lines demonstrated cytotoxicity against NH-1 in an major histocompatibility complex-dependent manner. Finally, we established two independent CD4(+) T-cell clones restricted to HLA-DR. The CD4(+) T-cell line responded strongly to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCL) but not to autologous normal cells. Furthermore, the T-cell clones also responded to allogeneic EBV-LCLs and B-ALL cell lines in the context of the HLA-DRB1( *)04051 molecule. Interestingly, 293T and COS-7 cells, which had been transfected with the HLA-DRB1( *)04051, were also recognized by T-cell clones.


CONCLUSIONS
These findings indicate that B-ALL has shared and strong immunogenic epitopes expressed on HLA class II molecules, the expression of which is limited to immortalized cells. These data suggest that vaccinations using DCs loaded with apoptotic tumor cells might be a potent strategy in the treatment of B-ALL.
Hatakeyama
Naoki
N
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tamura
Yasuaki
Y
Sahara
Hiroeki
H
Suzuki
Nobuhiro
N
Suzuki
Kazuhiko
K
Hori
Tsukasa
T
Mizue
Nobuo
N
Torigoe
Toshihiko
T
Tsutsumi
Hiroyuki
H
Sato
Noriyuki
N
D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000145:classification / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*
D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II