Abstract
IL-2 is a cytokine with multiple and even divergent functions; it has been described as a key cytokine for in vitro T cell proliferation but is also essential for down-regulating T cell responses by inducing activation-induced cell death as well as regulatory T cells. The in vivo analysis of IL-2 function in regulating specific T cell responses has been hampered by the fact that mice deficient in IL-2 or its receptors develop lymphoproliferative diseases and/or autoimmunity. Here we generated chimeric mice harboring both IL-2R-competent and IL-2R-deficient T cells and assessed CD8+ T cell induction, function and maintenance after acute or persistent viral infections. Induction and maintenance of CD8+ T cells were relatively independent of IL-2R signaling during acute/resolved viral infection. In marked contrast, IL-2 was crucial for secondary expansion of memory CD8+ T cells and for the maintenance of virus-specific CD8+ T cells during persistent viral infections. Thus, depending on the chronicity of antigen exposure, IL-2R signaling is either essential or largely dispensable for induction and maintenance of virus-specific CD8+ T cell responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Antigens, Viral / immunology
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Bone Marrow Transplantation
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / transplantation
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Chronic Disease
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Epitopes, T-Lymphocyte / immunology
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Glycoproteins / immunology
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Interferon-gamma / metabolism
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Interleukin-2 / metabolism
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Interleukin-2 Receptor alpha Subunit / genetics
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Interleukin-2 Receptor alpha Subunit / physiology
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Interleukin-7 Receptor alpha Subunit / metabolism
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L-Selectin / metabolism
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Lymphocyte Activation / immunology
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Lymphocytic choriomeningitis virus / immunology
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Lysosomal Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Peptide Fragments / immunology
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Interleukin-2 / genetics
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Receptors, Interleukin-2 / physiology*
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Signal Transduction*
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Tumor Necrosis Factor-alpha / metabolism
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Viral Proteins / immunology
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Virus Diseases / immunology*
Substances
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Antigens, Viral
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Epitopes, T-Lymphocyte
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Glycoproteins
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Interleukin-2
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Interleukin-2 Receptor alpha Subunit
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Interleukin-7 Receptor alpha Subunit
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Lysosomal Membrane Proteins
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-2
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Tumor Necrosis Factor-alpha
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
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L-Selectin
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Interferon-gamma