DOI: 10.1101/490789Dec 13, 2018Paper

High-dimensional characterization of IL-10 production and IL-10 dependent regulation during primary gammaherpesvirus infection

BioRxiv : the Preprint Server for Biology
Abigail K. KimballEric T. Clambey


Interleukin (IL)-10 is a potent immunomodulatory cytokine produced by multiple cell types to restrain immune activation. Many herpesviruses have utilized the IL-10 pathway to facilitate infection, but how endogenous IL-10 is regulated during primary infection in vivo remains poorly characterized. Here, we infected mice with murine gammaherpesvirus 68 (γHV68) and analyzed the production, and genetic contribution, of IL-10 using mass cytometry, or cytometry by time-of-flight (CyTOF), analysis. γHV68 infection elicited a breadth of effector CD4 T cells in the lungs of acutely infected mice, including a highly activated effector subset that co-expressed IFNγ, TNFα, and IL-10. By using IL-10 green fluorescent protein (gfp) transcriptional reporter mice, we identified that IL-10 was primarily expressed within CD4 T cells during acute infection in the lungs. IL10gfp expressing CD4 T cells were highly proliferative and characterized by the expression of multiple co-inhibitory receptors including PD-1 and LAG-3. When we analyzed acute γHV68 infection of IL-10 deficient mice, we found that IL-10 limits the frequency of both myeloid and effector CD4 T cell subsets in the infected lung, with minimal changes at a distant mucosal site. These...Continue Reading

Related Concepts

Laboratory mice
CD4 Positive T Lymphocytes
Transcription, Genetic
T-Lymphocyte Subsets
Green Fluorescent Proteins

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