The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29488879.
- Also identified by DOI 10.7554/eLife.30496 and PMC identifier 5844691.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Cytotoxic CD4 (CD4<sub>CTX</sub>) T cells are emerging as an important component of antiviral and antitumor immunity, but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant proportion of CD4 T cells displays cytotoxic functions. We observed that the transcriptional program of these cells was enriched in CD8 T cell lineage genes despite the absence of ThPOK downregulation. We further show that establishment of CD4<sub>CTX</sub>-specific transcriptional and epigenetic programs occurred in a stepwise fashion along the Th1-differentiation pathway. In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK. This work elucidates the molecular program of human CD4<sub>CTX</sub> T cells and identifies potential targets for immunotherapy against viral infections and cancer.
Medical subject headings
- Cell Differentiation
- Core Binding Factor Alpha 3 Subunit
- Cytomegalovirus Infections
- DNA-Binding Proteins
- T-Lymphocyte Subsets
- T-Lymphocytes, Cytotoxic
- Th1 Cells
- Transcription Factors