Abstract
Vascular endothelial growth factor (VEGF) is a proangiogenic mediator that promotes tumor growth. The role of VEGF in T lymphocytes is unknown. We found that T lymphocytes activated by either anti-CD3 monoclonal antibody (mAb) plus anti-CD28 mAb or by antigens on antigen-presenting cells transcribed mRNA for VEGF receptor 1 (VEGFR1) and VEGFR2. However, only VEGFR1 was expressed on the T cell surface. The addition of VEGF to either resting or activated T cells did not affect their proliferation, but VEGF increased IL-10 production and slightly decreased IFN-gamma production. A chemotaxis assay revealed that activated T lymphocytes migrate in response to VEGF. Our data suggest that VEGF has a direct immunomodulatory effect on T cells. Engagement of a high concentration of VEGF with VEGFR1 on T cells may cause T cells to migrate to tumor sites, and this interaction may play a role in IL-10-mediated immune evasion by tumor cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Cell Line
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Cell Proliferation / drug effects
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Chemotaxis, Leukocyte / drug effects*
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DNA Primers / genetics
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Humans
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Immunologic Factors / pharmacology*
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Immunotherapy
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In Vitro Techniques
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Interferon-gamma / biosynthesis
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Interleukin-10 / biosynthesis*
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Lymphocyte Activation
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Male
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Mice
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Mice, Inbred C57BL
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Models, Immunological
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Neoplasms / immunology
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Neoplasms / therapy
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects*
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T-Lymphocytes / immunology*
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T-Lymphocytes / physiology
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Vascular Endothelial Growth Factor A / pharmacology*
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-1 / metabolism
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Vascular Endothelial Growth Factor Receptor-2 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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DNA Primers
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Immunologic Factors
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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Interleukin-10
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Interferon-gamma
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2