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Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase
by
Suh, Woong-Kyung
, Gigoux, Mathieu
, Mak, Tak W
, Xu, Minghong
, Choe, Jongseon
, Shang, Jijun
, Pak, Youngshil
in
Animals
/ Antibodies
/ antibody affinity
/ Antigens, Differentiation, T-Lymphocyte - immunology
/ Antigens, Differentiation, T-Lymphocyte - metabolism
/ B lymphocytes
/ Biological Sciences
/ Blasts
/ CD28 Antigens - immunology
/ CD28 Antigens - metabolism
/ CD4-positive T-lymphocytes
/ CD4-Positive T-Lymphocytes - metabolism
/ Cell differentiation
/ Cell Differentiation - immunology
/ Cells
/ Cytokines
/ Enzyme-Linked Immunosorbent Assay
/ Immunoglobulins
/ Immunoprecipitation
/ Inducible T-Cell Co-Stimulator Protein
/ interleukin-21
/ interleukin-4
/ Interleukin-4 - immunology
/ Interleukins - immunology
/ Kinases
/ Ligation
/ Lymphoid tissue
/ Mice
/ Mice, Transgenic
/ phosphatidylinositol 3-kinase
/ Phosphatidylinositol 3-Kinases - immunology
/ Phosphatidylinositol 3-Kinases - metabolism
/ Receptors
/ Rodents
/ Signal transduction
/ Signal Transduction - immunology
/ T cell antigen receptors
/ T lymphocytes
/ T-Lymphocytes, Helper-Inducer - immunology
2009
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Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase
by
Suh, Woong-Kyung
, Gigoux, Mathieu
, Mak, Tak W
, Xu, Minghong
, Choe, Jongseon
, Shang, Jijun
, Pak, Youngshil
in
Animals
/ Antibodies
/ antibody affinity
/ Antigens, Differentiation, T-Lymphocyte - immunology
/ Antigens, Differentiation, T-Lymphocyte - metabolism
/ B lymphocytes
/ Biological Sciences
/ Blasts
/ CD28 Antigens - immunology
/ CD28 Antigens - metabolism
/ CD4-positive T-lymphocytes
/ CD4-Positive T-Lymphocytes - metabolism
/ Cell differentiation
/ Cell Differentiation - immunology
/ Cells
/ Cytokines
/ Enzyme-Linked Immunosorbent Assay
/ Immunoglobulins
/ Immunoprecipitation
/ Inducible T-Cell Co-Stimulator Protein
/ interleukin-21
/ interleukin-4
/ Interleukin-4 - immunology
/ Interleukins - immunology
/ Kinases
/ Ligation
/ Lymphoid tissue
/ Mice
/ Mice, Transgenic
/ phosphatidylinositol 3-kinase
/ Phosphatidylinositol 3-Kinases - immunology
/ Phosphatidylinositol 3-Kinases - metabolism
/ Receptors
/ Rodents
/ Signal transduction
/ Signal Transduction - immunology
/ T cell antigen receptors
/ T lymphocytes
/ T-Lymphocytes, Helper-Inducer - immunology
2009
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Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase
by
Suh, Woong-Kyung
, Gigoux, Mathieu
, Mak, Tak W
, Xu, Minghong
, Choe, Jongseon
, Shang, Jijun
, Pak, Youngshil
in
Animals
/ Antibodies
/ antibody affinity
/ Antigens, Differentiation, T-Lymphocyte - immunology
/ Antigens, Differentiation, T-Lymphocyte - metabolism
/ B lymphocytes
/ Biological Sciences
/ Blasts
/ CD28 Antigens - immunology
/ CD28 Antigens - metabolism
/ CD4-positive T-lymphocytes
/ CD4-Positive T-Lymphocytes - metabolism
/ Cell differentiation
/ Cell Differentiation - immunology
/ Cells
/ Cytokines
/ Enzyme-Linked Immunosorbent Assay
/ Immunoglobulins
/ Immunoprecipitation
/ Inducible T-Cell Co-Stimulator Protein
/ interleukin-21
/ interleukin-4
/ Interleukin-4 - immunology
/ Interleukins - immunology
/ Kinases
/ Ligation
/ Lymphoid tissue
/ Mice
/ Mice, Transgenic
/ phosphatidylinositol 3-kinase
/ Phosphatidylinositol 3-Kinases - immunology
/ Phosphatidylinositol 3-Kinases - metabolism
/ Receptors
/ Rodents
/ Signal transduction
/ Signal Transduction - immunology
/ T cell antigen receptors
/ T lymphocytes
/ T-Lymphocytes, Helper-Inducer - immunology
2009
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Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase
Journal Article
Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase
2009
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Overview
The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (TFH) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known that CD28-mediated PI3K activation is dispensable for GC reaction, the role of ICOS-driven PI3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate PI3K through ICOS had severe defects in TFH generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4⁺ T cells, ICOS delivered a potent PI3K signal that was critical for the induction of the key TFH cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate PI3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of TFH and suggest that CD28 and ICOS play differential roles during a multistep process of TFH differentiation.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Antigens, Differentiation, T-Lymphocyte - immunology
/ Antigens, Differentiation, T-Lymphocyte - metabolism
/ Blasts
/ CD4-Positive T-Lymphocytes - metabolism
/ Cell Differentiation - immunology
/ Cells
/ Enzyme-Linked Immunosorbent Assay
/ Inducible T-Cell Co-Stimulator Protein
/ Kinases
/ Ligation
/ Mice
/ phosphatidylinositol 3-kinase
/ Phosphatidylinositol 3-Kinases - immunology
/ Phosphatidylinositol 3-Kinases - metabolism
/ Rodents
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