Abstract
Interferon- (IFN-) γ is an essential cytokine for immunity against intracellular pathogens and cancer. IFN-γ expression by CD4 T lymphocytes is observed only after T helper (Th) 1 differentiation and there are several studies about the molecular mechanisms that control Ifng expression in these cells. However, naïve CD8 T lymphocytes do not produce large amounts of IFN-γ, but after TCR stimulation there is a progressive acquisition of IFN-γ expression during differentiation into cytotoxic T lymphocytes (CTL) and memory cells, which are capable of producing high levels of this cytokine. Differential gene expression can be regulated from the selective action of transcriptional factors and also from epigenetic mechanisms, such as DNA CpG methylation or posttranslational histone modifications. Recently it has been recognized that epigenetic modification is an integral part of CD8 lymphocyte differentiation. This review will focus on the chromatin status of Ifng promoter in CD8 T cells and possible influences of epigenetic modifications in Ifng gene and conserved noncoding sequences (CNSs) in regulation of IFN-γ production by CD8 T lymphocytes.
Highlights
IFN-γ Production by CD8 T LymphocytesCD8 T cells are usually characterized by their cytolytic activities involving perforin or Fas mechanisms to kill targeted cells
Interferon- (IFN-) γ is an essential cytokine for immunity against intracellular pathogens and cancer
Naıve CD8 T lymphocytes do not produce large amounts of IFN-γ, but after TCR stimulation there is a progressive acquisition of IFN-γ expression during differentiation into cytotoxic T lymphocytes (CTL) and memory cells, which are capable of producing high levels of this cytokine
Summary
CD8 T cells are usually characterized by their cytolytic activities involving perforin or Fas mechanisms to kill targeted cells. This work suggested that NFAT1 transcription factor-dependent IFN-γ production by CD8 T cell is important during eosinophil migration to pleura in a pleurisy model, which suggests an important role for IFN-γ produced by CD8 T cells in the control of allergic diseases. Together these studies reinforce the role of IFN-γ produced by CD8 T cells in regulation of Th immune responses in vivo. A previous paper has shown that naıve CD8 T cells receive an IFN-γ signal few hours after L. monocytogenes infection [23] These studies suggest that the IFN-γ signals for CD8 T cell differentiation are delivered early in the immune response. Regulation of Ifng expression in CD8 T cells is not fairly explored and discussed
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