Epigenetic Control of Interferon-Gamma Expression in CD8 T Cells

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.

Modulatory effects of levamisole and garlic oil on the immune response of Wistar rats: Biochemical, immunohistochemical, molecular and immunological study

“…Co-administration of LEVA and GO modulated the rats' immune response towards a Th1/Th2 balance; therefore, maintaining the body's defensive mechanisms within normal ranges. IFN-γ is an essential cytokine for immunity against intracellular pathogens and cancer (23). Targeted disruptions of the IFN-γ gene or IFN-γ receptor 1 gene in mice render them highly susceptible to bacterial, protozoan and viral infections (24).…”

“…Targeted disruptions of the IFN-γ gene or IFN-γ receptor 1 gene in mice render them highly susceptible to bacterial, protozoan and viral infections (24). The role of IFN-γ in CD8 T cell cellular immunity is to enhance the major histocompatibility complex class I antigen presentation pathway, which facilitates cytotoxic T cells to recognize infected cells (23). In the present study, the elevated levels of IFN-γ detected following LEVA treatment indicated its immunostimulatory effect towards induction and activation of Th1 cells, as reported in a previous Figure 3.…”

Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

“…Further evidences suggest that modifications of histones that lead to nucleosomal structural changes occur more often than in promoters regions [21]. For IFN-γ, modifications were detected at conserved noncoding sequences 1 (CNS1), CNS2, and Intron 3 [21,22,23].…”

“…For IFN-γ, modifications were detected at conserved noncoding sequences 1 (CNS1), CNS2, and Intron 3 [21,22,23]. Thus, in addition to the promoter site, we also determined the H3K9, H3K14 acetylation, and H3K36me3 levels at the CNS1, CNS2, and Intron 3 sites within the ifng locus of rat spleen with prenatal dexamethasone or postnatal HF diet exposure.…”

Mice lack of LRG-47 display the attenuated outcome of infection with Schistosoma japonicum

“…Additionally, the proportion of Tc1 cells in LRG-47 −/− mice was significantly higher than that in WT mice. It suggested that the function of CD8 + T cell might be enhanced and IFN-γ produced by CD8 + T cells promoted the cytolytic activity (de Araujo-Souza et al 2015). Earlier studies suggested that in the chronic phase of Schistosoma mansoni infection, the increased CD8 + T cells contributed to downregulate granulomatous reaction of the existing and new-formed granulomas in the livers (Fidel and Boros 1990;Ragheb and Boros 1989).…”