Abstract
T cell proliferation and survival are regulated by the cytokine receptor common gamma-chain-associated cytokines IL-2, IL-7, and IL-15, while IL-4, another gamma-chain-associated cytokine, is thought to primarily affect T cell quality rather than quantity. In contrast, our experiments reveal that endogenously produced IL-4 is a direct, nonredundant, and potent stimulator of CD8(+) T cell proliferation in Ag- and pathogen-induced CD8(+) T cell responses. These stimulatory effects of IL-4 are observed in both BALB/c and C57BL/6 mice and activate both naive and memory/activated phenotype CD8(+) T cells, although the former are stimulated less than are the latter. IL-4 effects are IL-7- and IL-15-independent, but MHC class I-dependent stimulation appears to be required for the mitogenic effect of IL-4 on naive phenotype CD8(+) T cells. Thus, endogenously produced IL-4 is an important regulator of quantitative as well as qualitative aspects of T cell immunity.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antigens, Dermatophagoides / administration & dosage
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Antigens, Dermatophagoides / immunology
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Bystander Effect / 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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Cell Death / immunology
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Cell Proliferation*
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Cell Survival / immunology
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Cells, Cultured
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Female
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / deficiency
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Growth Inhibitors / genetics
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Growth Inhibitors / physiology
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Interleukin-4 / biosynthesis*
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Interleukin-4 / deficiency
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Interleukin-4 / genetics
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Interleukin-4 / physiology*
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Nude
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Mice, SCID
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Mice, Transgenic
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / genetics
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Recombinant Proteins / pharmacology
Substances
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Antigens, Dermatophagoides
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Growth Inhibitors
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Recombinant Proteins
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Interleukin-4