title: Molecular control of CD4(+) T cell lineage plasticity and integrity.
abstract: CD4(+) helper T cells and CD8(+) cytotoxic T cells form the two major subsets of peripheral T lymphocytes. Helper T cells fulfill crucial roles in the activation and coordination of the immune response, while cytotoxic T cells kill virus-infected or tumor cells. Recent data suggest that the lineage identify of helper T cells is not fixed and that CD4(+) T cells under certain physiological conditions can be reprogrammed to express CD8 lineage genes and to develop into intestinal intraepithelial CD4(+) cytotoxic T lymphocytes that lack the expression of the key helper T cell lineage commitment factor ThPOK. Moreover, the analysis of mice with a conditional deletion of the transcription factor ThPOK or the histone deacetylases HDAC1 and HDAC2 indicated that CD8 lineage genes are actively repressed in CD4(+) T cells in order to maintain the lineage integrity of helper T cells. In this review I summarize recent studies that indicate plasticity of CD4(+) T cells towards a CTL program and that demonstrate that ThPOK and HDAC1-HDAC2 are part of a transcriptional regulatory circuit that counteracts the activity of the transcription factor Runx3 to maintain CD4(+) T cell lineage integrity.
authors: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria. Electronic address: wilfried.ellmeier@meduniwien.ac.at.
authors: Wilfried
authors: W
authors: Ellmeier
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019070:Cell Lineage; D000066670:Cell Plasticity; D050657:Core Binding Factor alpha Subunits / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D056284:Histone Deacetylase 1 / Q000276:immunology; D056464:Histone Deacetylase 2 / Q000276:immunology; D006801:Humans; D007422:Intestines / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology
chemical_list: D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C484225:ZBTB7B protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
keywords: CD4(+) T cell lineage integrity; CD4(+) cytotoxic T cells (CD4(+) CTLs); Histone deacetylases; Intestinal intraepithelial lymphocytes; Runx3; ThPOK