Generation of cytotoxic T lymphocytes (CTL) with phorbol ester and calcium ionophore

Conference · Fri Mar 15 04:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5172764

Tuttle, T M; Bear, H D ^[1]

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1. Virginia Commonwealth Univ., Richmond (United States)

Stimulation of lymphocytes with viable tumor cells can induce cytotoxic T lymphocytes (CTL) against autologous tumor. However, sufficient numbers of tumor cells are not always available for such stimulation, and high dose interleukin-2 (IL-2) is often required for growth. Using the weakly immunogenic methylcholanthrene-induced sarcoma MCA105, the authors demonstrate here that CTLs can be expected by pharmacologic manipulation of protein kinase C (PKC) and intracellular calcium with phorbol dibutyrate (PD-Bu) and ionomycin (Io), respectively. Lymphocytes were obtained from the spleens and ipsilateral popliteal draining lymph nodes (DLN) 10 days after the footpad injection of viable MCA105 tumor cells. The cells were stimulated with autologous tumor and 20U/ml IL-2 for 7 days and then treated with PDBu and Io and expanded in culture with 20U/ml IL-2 for an additional 14 days. The lymphocytes from the spleens and DLNs demonstrated significant expansion and marked cytotoxicity against MCA105. In another regimen, lymphocytes from the DLNs of tumor-bearing mice were stimulated directly with PDBu and Io without prior in vitro exposure to autologous tumor and expanded in culture with 20U/ml IL-2. The expansion of these lymphocytes was 500 fold and the cytotoxicity against MCA 105 remained high. Lymphocytes expanded with PDBu and Io also killed MCA102, but normal spleen cells expanded in the same way had no cytotoxic activity. The authors conclude that PKC activators coupled with calcium ionophores and low-dose IL-2 can generate CTL when little or no antigen is available.

• OSTI ID: 5172764
• Report Number(s): CONF-9104107--
• Conference Information: Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 5:5
• Country of Publication: United States
• Language: English

Related Subjects

3-METHYLCHOLANTHRENE
560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METALS
ANIMAL CELLS
AROMATICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CALCIUM
CARCINOGENESIS
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CELL PROLIFERATION
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
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ELEMENTS
ENZYMES
ESTERS
GROWTH FACTORS
HYDROCARBONS
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MATERIALS
METALS
MITOGENS
NEOPLASMS
ORGANIC COMPOUNDS
PATHOGENESIS
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
POLYCYCLIC AROMATIC HYDROCARBONS
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SARCOMAS
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