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| Article Authors: | Shweta S Puntambekar; Cornelia C Bergmann; Carine Savarin; Christopher L Karp; Timothy W Phares; Gabriel I Parra; David R Hinton; Stephen A Stohlman |
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| Article Title: | Shifting Hierarchies of Interleukin-10-Producing T Cell Populations in the Central Nervous System during Acute and Persistent Viral Encephalomyelitis. |
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| Reference ID: | 1022084 |
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| Abstract: | Interleukin-10 (IL-10) mRNA is rapidly upregulated in the central nervous system (CNS) following infection with neurotropic coronavirus and remains elevated during persistent infection. Infection of transgenic IL-10/green fluorescent protein (GFP) reporter mice revealed that CNS-infiltrating T cells were the major source of IL-10, with minimal IL-10 production by macrophages and resident microglia. The proportions of IL-10-producing cells were initially similar in CD8(+) and CD4(+) T cells but diminished rapidly in CD8(+) T cells as the virus was controlled. Overall, the majority of IL-10-producing CD8(+) T cells were specific for the immunodominant major histocompatibility complex (MHC) class I epitope. Unlike CD8(+) T cells, a large proportion of CD4(+) T cells within the CNS retained IL-10 production throughout persistence. Furthermore, elevated frequencies of IL-10-producing CD4(+) T cells in the spinal cord supported preferential maintenance of IL-10 production at the site of viral persistence and tissue damage. IL-10 was produced primarily by the CD25(+) CD4(+) T cell subset during acute infection but prevailed in CD25(-) CD4(+) T cells during the transition to persistent infection and thereafter. Overall, these data demonstrate significant fluidity in the T-cell-mediated IL-10 response during viral encephalitis and persistence. While IL-10 production by CD8(+) T cells was limited primarily to the time of acute effector function, CD4(+) T cells continued to produce IL-10 throughout infection. Moreover, a shift from predominant IL-10 production by CD25(+) CD4(+) T cells to CD25(-) CD4(+) T cells suggests that a transition to nonclassical regulatory T cells precedes and is retained during CNS viral persistence. |
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| Affiliations: | Department of Neuroscience, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, NC30, Cleveland, OH 44195. stohlms2@ccf.org. |
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| Date: | 2011 |
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| Reference Type: | Literature |
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| PubMed ID: | 21525347 |
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| Journal: | J Virol |
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| Journal Volume: | 85 |
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| Article Pages: | 6702-13 |
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| Journal ISSN: | 1098-5514 |
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| Curation Last Updated: | 2013-05-28 22:27:04 |
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