Abstract
The presence of IL-12 during antigen stimulation instructs naive CD8+ T cells for long-term effector responses, but their mechanisms of collaboration are not understood completely. Herein, we report that CD8+ T cells (OT-I T cells) stimulated with antigen for a longer duration show enhanced sensitization to IL-12 as a result of Erk1/2-dependent, increased Ets-1 phosphorylation and subsequent increases in IL-12Rbeta2 expression. Correspondingly, naive OT-I T cells stimulated by antigen for a longer duration in the presence of IL-12, irrespective of frequency of APCs, show robust effector maturation and mount long-term antigen-recall responses upon adoptive transfer. These results identify the role of antigen strength-dependent Erk1/2 activation for Ets-1-mediated collaboration with IL-12 in CD8+ T cells.
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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Animals
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Antigens / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Enzyme Activation / drug effects
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Interleukin-12 / immunology*
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Interleukin-12 / pharmacology
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / immunology*
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / immunology*
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phosphorylation / drug effects
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Phosphorylation / genetics
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Phosphorylation / immunology
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Proto-Oncogene Protein c-ets-1 / genetics
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Proto-Oncogene Protein c-ets-1 / immunology*
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Proto-Oncogene Protein c-ets-1 / metabolism
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Receptors, Interleukin-12
Substances
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Antigens
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Ets1 protein, mouse
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Il12rb2 protein, mouse
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Proto-Oncogene Protein c-ets-1
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Receptors, Interleukin-12
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Interleukin-12
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Mapk1 protein, mouse
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3