CD8+ T Cell Response to Gammaherpesvirus Infection Mediates Inflammation and Fibrosis in Interferon Gamma Receptor-Deficient Mice

PloS One
Brigid M O'FlahertySamuel H Speck

Abstract

Idiopathic pulmonary fibrosis (IPF), one of the most severe interstitial lung diseases, is a progressive fibrotic disorder of unknown etiology. However, there is growing appreciation for the role of viral infection in disease induction and/or progression. A small animal model of multi-organ fibrosis, which involves murine gammaherpesvirus (MHV68) infection of interferon gamma receptor deficient (IFNγR-/-) mice, has been utilized to model the association of gammaherpesvirus infections and lung fibrosis. Notably, several MHV68 mutants which fail to induce fibrosis have been identified. Our current study aimed to better define the role of the unique MHV68 gene, M1, in development of pulmonary fibrosis. We have previously shown that the M1 gene encodes a secreted protein which possesses superantigen-like function to drive the expansion and activation of Vβ4+ CD8+ T cells. Here we show that M1-dependent fibrosis is correlated with heightened levels of inflammation in the lung. We observe an M1-dependent cellular infiltrate of innate immune cells with most striking differences at 28 days-post infection. Furthermore, in the absence of M1 protein expression we observed reduced CD8+ T cells and MHV68 epitope specific CD8+ T cells to the...Continue Reading

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Citations

May 29, 2019·The Journal of Clinical Investigation·Alvaro C UceroErwin F Wagner
Jan 11, 2017·Particle and Fibre Toxicology·Christine SattlerTobias Stoeger
Feb 3, 2021·The Journal of General Virology·Leonardo P MesquitaPaulo C Maiorka
Jul 9, 2021·PloS One·Pratyusha MandalCraig M Coopersmith

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Methods Mentioned

BETA
flow cytometry
biopsies
PMA

Software Mentioned

GraphPad
FloJo

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