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Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1.


ABSTRACT: During the course of many chronic viral infections, the antiviral T cell response becomes attenuated through a process that is regulated in part by the host. While elevated expression of the immunosuppressive cytokine IL-10 is involved in the suppression of viral-specific T cell responses, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we traced IL-10 production over the course of chronic lymphocytic choriomeningitis virus (LCMV) infection in an IL-10 reporter mouse line. Using this model, we demonstrated that virus-specific T cells with reduced inflammatory function, particularly Th1 cells, display elevated and sustained IL-10 expression during chronic LCMV infection. Furthermore, ablation of IL-10 from the T cell compartment partially restored T cell function and reduced viral loads in LCMV-infected animals. We found that viral persistence is needed for sustained IL-10 production by Th1 cells and that the transcription factor BLIMP-1 is required for IL-10 expression by Th1 cells. Restimulation of Th1 cells from LCMV-infected mice promoted BLIMP-1 and subsequent IL-10 expression, suggesting that constant antigen exposure likely induces the BLIMP-1/IL-10 pathway during chronic viral infection. Together, these data indicate that effector T cells self-limit their responsiveness during persistent viral infection via an IL-10-dependent negative feedback loop.

SUBMITTER: Parish IA 

PROVIDER: S-EPMC4109559 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1.

Parish Ian A IA   Marshall Heather D HD   Staron Matthew M MM   Lang Philipp A PA   Brüstle Anne A   Chen Jonathan H JH   Cui Weiguo W   Tsui Yao-Chen YC   Perry Curtis C   Laidlaw Brian J BJ   Ohashi Pamela S PS   Weaver Casey T CT   Kaech Susan M SM  

The Journal of clinical investigation 20140708 8


During the course of many chronic viral infections, the antiviral T cell response becomes attenuated through a process that is regulated in part by the host. While elevated expression of the immunosuppressive cytokine IL-10 is involved in the suppression of viral-specific T cell responses, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we traced IL-10 production over the course of chronic lymphocytic choriomeningiti  ...[more]

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