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Identification of human progenitors of exhausted CD8+ T cells associated with elevated IFN-γ response in early phase of viral infection
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Identification of human progenitors of exhausted CD8+ T cells associated with elevated IFN-γ response in early phase of viral infection
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Journal Article
Identification of human progenitors of exhausted CD8+ T cells associated with elevated IFN-γ response in early phase of viral infection
2022
Overview
T cell exhaustion is a hallmark of hepatitis C virus (HCV) infection and limits protective immunity in chronic viral infections and cancer. Limited knowledge exists of the initial viral and immune dynamics that characterise exhaustion in humans. We studied longitudinal blood samples from a unique cohort of individuals with primary infection using single-cell multi-omics to identify the functions and phenotypes of HCV-specific CD8
+
T cells. Early elevated IFN-γ response against the transmitted virus is associated with the rate of immune escape, larger clonal expansion, and early onset of exhaustion. Irrespective of disease outcome, we find heterogeneous subsets of progenitors of exhaustion, based on the level of PD-1 expression and loss of AP-1 transcription factors. Intra-clonal analysis shows distinct trajectories with multiple fates and evolutionary plasticity of precursor cells. These findings challenge the current paradigm on the contribution of CD8
+
T cells to HCV disease outcome and provide data for future studies on T cell differentiation in human infections.
The early immune response following exposure to HCV is not fully explored. Here the authors use single cell analysis and immune profiling to relate the infection sequence and immune response to early HCV infection showing that exhausted phenotypes of T cells arise early post infection.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
