Abstract
The beta-herpesvirus CMV induces a substantial and progressive expansion of virus-specific memory CD8 T cells, which protect the host against viral reactivation from latency. In this paper, we report that this expansion, or "inflation," of memory T cells is amplified dramatically during mouse CMV infection of IL-10 knockout (IL-10(-/-)) mice. T cells from IL-10(-/-) mice were oligoclonal, exhibited a highly activated phenotype, expressed antiviral cytokines, and degranulated in response to cognate Ag encounter ex vivo. Moreover, latent viral load was reduced in IL-10(-/-) mice. Importantly, these results were recapitulated by IL-10R blockade during chronic/latent infection of wild-type mice. These data demonstrate that regulatory immune mechanisms can influence CMV-specific T cell memory and suggest a possible rationale for the acquisition of functional IL-10 orthologs by herpesviruses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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BALB 3T3 Cells
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / virology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Chronic Disease
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Epitopes, T-Lymphocyte / immunology
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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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Herpesviridae Infections / immunology*
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Herpesviridae Infections / pathology*
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Immunologic Memory*
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Interleukin-10 / deficiency
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Interleukin-10 / genetics
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Interleukin-10 / physiology*
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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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Molecular Sequence Data
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Muromegalovirus / immunology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / pathology*
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T-Lymphocyte Subsets / virology
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Virus Latency / immunology
Substances
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Epitopes, T-Lymphocyte
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Growth Inhibitors
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Interleukin-10