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Paracrine costimulation of IFN-γ signaling by integrins modulates CD8 T cell differentiation
by
Gérard, Audrey
, Mazet, Julie M.
, Krummel, Matthew F.
, Gartner, Zev J.
, Mahale, Jagdish N.
, Uhl, Lion F. K.
, Weber, Robert J.
, Mujal, Adriana M.
, Hardison, Emily A.
in
Animals
/ Bacterial diseases
/ Biological Sciences
/ CD8 antigen
/ CD8-Positive T-Lymphocytes - drug effects
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - microbiology
/ Cell differentiation
/ Cell Differentiation - drug effects
/ Cell Differentiation - immunology
/ Cell interactions
/ Cells
/ Cellular biology
/ Cellular Microenvironment
/ Cofactors
/ Cytokines
/ Differentiation (biology)
/ Down-regulation
/ Immune system
/ Immunologic Memory
/ Immunological memory
/ Immunological Synapses
/ Immunology and Inflammation
/ Integrins
/ Integrins - immunology
/ Interferon-gamma - immunology
/ Interferon-gamma - pharmacology
/ Interleukin 2
/ Interleukin 2 receptors
/ Killer Cells, Natural - drug effects
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - microbiology
/ Leukocytes
/ Listeria monocytogenes - growth & development
/ Listeria monocytogenes - immunology
/ Lymph Nodes - cytology
/ Lymph Nodes - immunology
/ Lymphocyte Activation - drug effects
/ Lymphocytes
/ Lymphocytes T
/ Mice
/ Mice, Inbred C57BL
/ Natural killer cells
/ Paracrine Communication - immunology
/ Paracrine signalling
/ Phosphorylation
/ Primary Cell Culture
/ Signal Transduction
/ Spleen
/ Spleen - cytology
/ Spleen - immunology
/ Stat1 protein
/ Synapses
/ Tetradecanoylphorbol Acetate - pharmacology
/ γ-Interferon
2018
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Paracrine costimulation of IFN-γ signaling by integrins modulates CD8 T cell differentiation
by
Gérard, Audrey
, Mazet, Julie M.
, Krummel, Matthew F.
, Gartner, Zev J.
, Mahale, Jagdish N.
, Uhl, Lion F. K.
, Weber, Robert J.
, Mujal, Adriana M.
, Hardison, Emily A.
in
Animals
/ Bacterial diseases
/ Biological Sciences
/ CD8 antigen
/ CD8-Positive T-Lymphocytes - drug effects
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - microbiology
/ Cell differentiation
/ Cell Differentiation - drug effects
/ Cell Differentiation - immunology
/ Cell interactions
/ Cells
/ Cellular biology
/ Cellular Microenvironment
/ Cofactors
/ Cytokines
/ Differentiation (biology)
/ Down-regulation
/ Immune system
/ Immunologic Memory
/ Immunological memory
/ Immunological Synapses
/ Immunology and Inflammation
/ Integrins
/ Integrins - immunology
/ Interferon-gamma - immunology
/ Interferon-gamma - pharmacology
/ Interleukin 2
/ Interleukin 2 receptors
/ Killer Cells, Natural - drug effects
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - microbiology
/ Leukocytes
/ Listeria monocytogenes - growth & development
/ Listeria monocytogenes - immunology
/ Lymph Nodes - cytology
/ Lymph Nodes - immunology
/ Lymphocyte Activation - drug effects
/ Lymphocytes
/ Lymphocytes T
/ Mice
/ Mice, Inbred C57BL
/ Natural killer cells
/ Paracrine Communication - immunology
/ Paracrine signalling
/ Phosphorylation
/ Primary Cell Culture
/ Signal Transduction
/ Spleen
/ Spleen - cytology
/ Spleen - immunology
/ Stat1 protein
/ Synapses
/ Tetradecanoylphorbol Acetate - pharmacology
/ γ-Interferon
2018
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Paracrine costimulation of IFN-γ signaling by integrins modulates CD8 T cell differentiation
by
Gérard, Audrey
, Mazet, Julie M.
, Krummel, Matthew F.
, Gartner, Zev J.
, Mahale, Jagdish N.
, Uhl, Lion F. K.
, Weber, Robert J.
, Mujal, Adriana M.
, Hardison, Emily A.
in
Animals
/ Bacterial diseases
/ Biological Sciences
/ CD8 antigen
/ CD8-Positive T-Lymphocytes - drug effects
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - microbiology
/ Cell differentiation
/ Cell Differentiation - drug effects
/ Cell Differentiation - immunology
/ Cell interactions
/ Cells
/ Cellular biology
/ Cellular Microenvironment
/ Cofactors
/ Cytokines
/ Differentiation (biology)
/ Down-regulation
/ Immune system
/ Immunologic Memory
/ Immunological memory
/ Immunological Synapses
/ Immunology and Inflammation
/ Integrins
/ Integrins - immunology
/ Interferon-gamma - immunology
/ Interferon-gamma - pharmacology
/ Interleukin 2
/ Interleukin 2 receptors
/ Killer Cells, Natural - drug effects
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - microbiology
/ Leukocytes
/ Listeria monocytogenes - growth & development
/ Listeria monocytogenes - immunology
/ Lymph Nodes - cytology
/ Lymph Nodes - immunology
/ Lymphocyte Activation - drug effects
/ Lymphocytes
/ Lymphocytes T
/ Mice
/ Mice, Inbred C57BL
/ Natural killer cells
/ Paracrine Communication - immunology
/ Paracrine signalling
/ Phosphorylation
/ Primary Cell Culture
/ Signal Transduction
/ Spleen
/ Spleen - cytology
/ Spleen - immunology
/ Stat1 protein
/ Synapses
/ Tetradecanoylphorbol Acetate - pharmacology
/ γ-Interferon
2018
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Paracrine costimulation of IFN-γ signaling by integrins modulates CD8 T cell differentiation
Journal Article
Paracrine costimulation of IFN-γ signaling by integrins modulates CD8 T cell differentiation
2018
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Overview
The cytokine IFN-γ is a critical regulator of immune system development and function. Almost all leukocytes express the receptor for IFN-γ, yet each cell type elicits a different response to this cytokine. Cell type-specific effects of IFN-γ make it difficult to predict the outcomes of the systemic IFN-γ blockade and limit its clinical application, despite many years of research. To better understand the cell–cell interactions and cofactors that specify IFN-γ functions, we focused on the function of IFN-γ on CD8 T cell differentiation. We demonstrated that during bacterial infection, IFN-γ is a dominant paracrine trigger that skews CD8 T cell differentiation toward memory. This skewing is preferentially driven by contact-dependent T cell–T cell (T-T) interactions and the localized IFN-γ secretion among activated CD8 T cells in a unique splenic microenvironment, and is less sensitive to concurrent IFN-γ production by other immune cell populations such as natural killer (NK) cells. Modulation of CD8 T cell differentiation by IFN-γ relies on a nonconventional IFN-γ outcome that occurs specifically within 24 hours following infection. This is driven by IFN-γ costimulation by integrins at T-T synapses, and leads to synergistic phosphorylation of the proximal STAT1 molecule and accelerated IL-2 receptor down-regulation. This study provides evidence of the importance of context-dependent cytokine signaling and gives another example of how cell clusters and the microenvironment drive unique biology.
Publisher
National Academy of Sciences
Subject
/ CD8-Positive T-Lymphocytes - drug effects
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - microbiology
/ Cell Differentiation - drug effects
/ Cell Differentiation - immunology
/ Cells
/ Interferon-gamma - immunology
/ Interferon-gamma - pharmacology
/ Killer Cells, Natural - drug effects
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - microbiology
/ Listeria monocytogenes - growth & development
/ Listeria monocytogenes - immunology
/ Lymphocyte Activation - drug effects
/ Mice
/ Paracrine Communication - immunology
/ Spleen
/ Synapses
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