BioProject

HBV-specific CD8 cells are deeply exhausted in chronic hepatitis B and their function can only be partially corrected by modulation of up-regulated inhibitory pathways, suggesting a more complex molecular interplay. More...

HBV-specific CD8 cells are deeply exhausted in chronic hepatitis B and their function can only be partially corrected by modulation of up-regulated inhibitory pathways, suggesting a more complex molecular interplay. With the aim of identifying more suitable molecular targets to correct T cell dysfunction, we compared the transcriptome profile of HBV-specific CD8 cells of acute and chronic patients with the reference profile of HBV- and Flu-specific CD8 cells from patients able to resolve HBV infection spontaneously and from healthy subjects. The results indicate that exhausted HBV-specific CD8 cells are deeply impaired at a metabolic and energetic level with a prevalent down-regulation of different key cellular processes centered on an extensive alteration of mitocondrial functions. Mitochondrial modulation by antioxidant compounds could improve significantly the HBV-specific T cell function with minimal effect on T cells of different specificity. The results identify mitochondria as ideal targets for functional T cell reconstitution strategies to cure HBV infection Overall design: Virus-specific CD8+ T cells were isolated and sorted from four (chronic, resolved), five (acute) different patients and from five healthy donors. RNA from sorted CD8+ T cells was processed, amplified, labeled, and hybridized to Agilent microarrays. Less...