Abstract
Monocytes differentiate into dendritic cells (DC) in response to GM-CSF combined with other cytokines including IL-4 and IL-15. Here, we show that IL15-DC are efficient in priming naive CD8+ T cells to differentiate into melanoma antigen-specific cytotoxic T lymphocytes (CTL). While both melanoma peptide-pulsed IL15-DC and IL4-DC expand high-precursor frequency MART-1-specific CD8+ T cells after two stimulations in vitro, IL15-DC require much lower peptide concentration for priming. IL15-DC are more efficient in expanding gp100-specific CD8+ T cells and can expand CD8+ T cells specific for Tyrosinase and MAGE-3. CTL primed by IL15-DC are superior in their function as demonstrated by (i) higher IFN-gamma secretion, (ii) higher expression of Granzyme B and Perforin, and (iii) higher killing of allogeneic melanoma cell lines, most particularly the HLA-A*0201+ Sk-Mel-24 melanoma cells that are resistant to killing by CD8+ T cells primed with IL4-DC. Supernatants of the sonicated cells demonstrate unique expression of IL-1, IL-8 and IL-15. Therefore, membrane-bound IL-15 might contribute to enhanced priming by IL15-DC. Thus, IL-15 induces myeloid DC that are efficient in priming and maturation of melanoma antigen-specific CTL.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / analysis
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Antigens, CD / metabolism
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Antigens, Neoplasm / immunology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / immunology*
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Cell Line, Tumor
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Cell Proliferation
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Coculture Techniques
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Cytotoxicity Tests, Immunologic
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Granzymes / metabolism
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Humans
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Interferon-gamma / metabolism
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Interleukin-1 / metabolism
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Interleukin-15 / metabolism
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Interleukin-15 / pharmacology*
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Interleukin-4 / metabolism
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Interleukin-4 / pharmacology
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Interleukin-8 / metabolism
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K562 Cells
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Leukocyte Common Antigens / metabolism
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Lipopolysaccharides / pharmacology
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Lymphocytes / cytology
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Lymphocytes / immunology
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Lymphocytes / metabolism
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Melanoma / immunology*
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Monocytes / cytology
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Monocytes / immunology
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Monocytes / metabolism
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Monophenol Monooxygenase / immunology
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Neoplasm Proteins / immunology
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Receptors, CCR7
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Receptors, Chemokine / metabolism
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T-Lymphocytes, Cytotoxic / immunology*
Substances
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Antigens, CD
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Antigens, Neoplasm
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CCR7 protein, human
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Interleukin-1
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Interleukin-15
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Interleukin-8
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Lipopolysaccharides
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MAGEA3 protein, human
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Neoplasm Proteins
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Receptors, CCR7
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Receptors, Chemokine
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Interleukin-4
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Interferon-gamma
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Monophenol Monooxygenase
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Leukocyte Common Antigens
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Granzymes