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Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection
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Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection
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Journal Article
Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection
2019
Overview
Progenitor-like CD8
+
T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct programs to adapt to the immunosuppressive environment. By comparing the single-cell transcriptomes and epigenetic profiles of CD8
+
T cells responding to acute and chronic viral infections, we found that progenitor-like CD8
+
T cells became distinct from memory precursor cells before the peak of the T cell response. We discovered a coexpression gene module containing
Tox
that exhibited higher transcriptional activity associated with more abundant active histone marks in progenitor-like cells than memory precursor cells. Moreover, thymocyte selection-associated high mobility group box protein TOX (TOX) promoted the persistence of antiviral CD8
+
T cells and was required for the programming of progenitor-like CD8
+
T cells. Thus, long-term CD8
+
T cell immunity to chronic viral infection requires unique transcriptional and epigenetic programs associated with the transcription factor TOX.
Long-lived, self-renewing ‘progenitor-like’ CD8
+
T cells can arise during chronic viral infection or in cancer. Wu and colleagues identify the transcription factor TOX as essential to endow ‘stemness’ and long-term persistence in the face of chronic infection.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Chromatin Immunoprecipitation
/ High mobility group proteins
/ High-Throughput Nucleotide Sequencing
/ Histones
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Host-Pathogen Interactions - genetics
/ Host-Pathogen Interactions - immunology
/ Lymphocytic Choriomeningitis - immunology
/ Lymphocytic Choriomeningitis - virology
/ Lymphocytic choriomeningitis virus - immunology
/ Mice
/ RNA
