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KMID : 0942820080070020150
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Journal of Korean Brain Tumor Society
2008 Volume.7 No. 2 p.150 ~ p.155
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HLA-Restricted Cytotoxicity of Tumor-Specific T Lymphocytes Induced by Malignant Glioma Apoptotic Body-Pulsed Human Dendritic Cells
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Park Ik-Seong
Chung Dong-Sup
Han Young-Min
Jang Kyung-Sul
Kim Jong-Tae
Park Young-Sup
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Abstract
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Objective: The purpose of this study is to determine whether human dendritic cells(DCs) pulsed with glioma apoptotic bodies(GABs) can induce tumor-specific T lymphocytes having cytotoxicities to allogeneic glioma cells matched or mismatched at class I human leukocyte antigen(HLA) loci.
Methods: DCs were generated from peripheral blood mononuclear cells(PBMCs) of HLA-A2 positive healthy donors cultured in the presence of granulocyte macrophage-colony stimulating factor and interleukin(IL)-4. GABs from HLAA2 positive T98G glioblastoma cells following actinomycin D treatment were pulsed to DCs. CD8+ T lymphocytes
isolated from PBMCs of the same donors were cultured in media containing IL-2 and were stimulated by GAB-pulsed
DCs three times at weekly interval. Then cytolytic activities of these cytotoxic CD8+ T cells against HLA-A2 positive
T98G and U87 glioblastoma cells, and HLA-A2 negative A172 glioblastoma cells were determined by a standard 4hr
[51Cr]-release assay.
Results: The average percentages of T98G , U87 and A172 cell lysis were 43.7%, 45.6% and 5.1% compared with 3.6% of controls at an effector to target cell ratio of 40：1 respectively. The cytotoxic T lymphocytes(CTLs) primed with HLAA2 positive T98G GAB-pulsed DCs had cytotoxicity to HLA-A2 positive T98G and U87 glioma cells but not to HLAA2
negative A172 cells(p<0.01).
Conclusion: This study showed that tumor-specific CTLs generated by stimulations with GAB-pulsed DCs had cytotoxicity to the glioma cells in a HLA-restricted manner. This result suggests the feasibility of the use of HLA-matched
allogeneic glioma cells as a source of antigens for patients not eligible for surgery in the DC-based immunotherapy.
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KEYWORD
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Cytotoxicity, Dendritic cell, Glioma apoptotic body, Human leucocyte antigen, Allogeneic glioma cell
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