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Differentiation of exhausted CD8+ T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory
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Differentiation of exhausted CD8+ T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory
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Journal Article
Differentiation of exhausted CD8+ T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory
2021
Overview
T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Here we confirmed pervasive phenotypic, functional and transcriptional differences between memory and exhausted antigen-specific CD8
+
T cells in human hepatitis C virus (HCV) infection before and after treatment. After viral cure, phenotypic changes in clonally stable exhausted T cell populations suggested differentiation toward a memory-like profile. However, functionally, the cells showed little improvement, and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for less time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved HCV infection. Thus, the duration of T cell stimulation impacts exhaustion recovery, with antigen removal after long-term exhaustion being insufficient for the development of functional T cell memory.
Lauer and colleagues examine CD8
+
T cells following cure of human hepatitis C virus (HCV) infection. CD8
+
T cells exposed to chronic HCV-specific activation show durable functional, phenotypic and transcriptional exhaustion that is maintained even after antigen stimulus is removed.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Antigens
/ Antiviral Agents - therapeutic use
/ Biomedical and Life Sciences
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - pathology
/ Cell Differentiation - immunology
/ Hepatitis C, Chronic - drug therapy
/ Hepatitis C, Chronic - immunology
/ Humans
