Induction of Cellular Immune Response by Dendritic Cells Pulsed with Glioma Apoptotic Bodies.

Kim, In Su; Kim, Jong Tae; Cho, Hyun Il; Park, Young Sup; Kim, Moon Chan; Chung, Dong Sup

Original Article

Journal of Korean Neurosurgical Society 2003;34(4): 360-365.

In Su Kim, Jong Tae Kim, Hyun Il Cho, Young Sup Park, Moon Chan Kim, Dong Sup Chung

¹Department of Neurosurgery, College of Medicine, The Catholic University of Korea, Seoul, Korea. dschung@olmh.cuk.ac.kr
²Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

ABSTRACT

OBJECTIVE
The aim of this study is to verify the hypothesis that human dendritic cells(DCs) can process antigens from glioma cell apoptotic bodies and induce antigen-specific effector T cells. METHODS: DCs generated in the presence of granulocyte macrophage-colony stimulating factor(GM-CSF) and interleukin-4(IL-4) from peripheral blood mononuclear cells(PBMCs) of healthy donors with human leucocyte antigen(HLA) A*0201 were cultured for 7 days. Glioma apoptotic bodies(GABs) from T98G glioblastoma cells following 18 hour-actinomycin D treatment were co-incubated with DCs for 3 days. CD8 T cells isolated from peripheral blood of same donors were cultured in media containing IL-2 and were stimulated by GAB-pulsed DCs three times at a weekly interval. The interferon-gamma(IFN-gamma), a cytokine related to cytotoxicity, concentrations of cell culture supernates were measured by enzyme immunoassay technique.
RESULTS
Induced DCs had DC's own phenotypic characteristics such as highly expressed major histocompatibility complex(MHC) class II, CD1a and CD86 molecules. They also had high endocytotic activity. Preteatment of T98G glioma cells with actinomycin D resulted in 53% of cells undergoing apoptosis. IFN-gamma production of effector T cells stimulated by GAB-pulsed DCs was significantly higher than that of T cells stimulated by non-pulsed DCs. CONCLUSION: Naive CD8 T cells can be activated by human GAB-pulsed DCs to become antigen-specific effector T cells. Using GABs as a antigen source may be a novel approach in future DC-based immunotherapeutic trials for malignant glioma.

Key Words: Dendritic cell; Glioma apoptotic body; Interferon-gamma; Antigen-specific effector T cell; Immunotherapeutic trial