Cutting Edge: Polycomb Repressive Complex 1 Subunit Cbx4 Positively Regulates Effector Responses in CD8 T Cells.

CTL differentiation is controlled by the crosstalk of various transcription factors and epigenetic modulators. Uncovering this process is fundamental to improving immunotherapy and designing novel therapeutic approaches. In this study, we show that polycomb repressive complex 1 subunit chromobox (Cbx)4 favors effector CTL differentiation in a murine model. Cbx4 deficiency in CTLs induced a transcriptional signature of memory cells and increased the memory CTL population during acute viral infection. It has previously been shown that besides binding to H3K27me3 through its chromodomain, Cbx4 functions as a small ubiquitin-like modifier (SUMO) E3 ligase in a SUMO-interacting motifs (SIM)-dependent way. Overexpression of Cbx4 mutants in distinct domains showed that this protein regulates CTL differentiation primarily in an SIM-dependent way and partially through its chromodomain. Our data suggest a novel role of a polycomb group protein Cbx4 controlling CTL differentiation and indicated SUMOylation as a key molecular mechanism connected to chromatin modification in this process.

Differential interferon-γ production by naive and memory-like CD8 T cells.

CD8 T cells play a crucial role in immune responses to virus infections and tumors. Naïve CD8 T lymphocytes after TCR stimulation undergo differentiation into CTLs and memory cells, which are essential sources of IFN-γ. We investigated IFN-γ production by CD8 T cell subsets found in nonimmune mice. A minor fraction of in vitro TCR-stimulated CD8 T cells produce IFN-γ, and it is regulated at the transcriptional level. Antigen inexperienced C57BL/6 mice present the coexistence of 2 populations. The main population exhibits a CD44low CD122low profile, which is compatible with naïve lymphocytes. The minor expresses a phenotype of immunologic memory, CD44hi CD122hi . Both subsets are able to produce IL-2 in response to TCR activation, but only the memory-like population is responsible for IFN-γ production. Similar to memory CD8 T cells, CD44hi CD8+ T cells also present a higher level of the transcriptional factor Eomes and a lower level of T-bet (Tbx21) mRNA than CD44low CD8+ T cells. The presence of the CD44hi CD8+ T cell population in nonimmune OT-I transgenic mice reveals that the population is generated independently of antigenic stimulation. CpG methylation is an efficient epigenetic mechanism for gene silencing. DNA methylation at posttranscriptional CpG sites in the Ifng promoter is higher in CD44low CD8+ T cells than in CD44hi CD8+ T cells. Thus, memory-like CD8 T cells have a distinct epigenetic pattern in the Ifng promoter and can rapidly produce IFN-γ in response to TCR stimulation.

IRF2BP2: A new player in the regulation of cell homeostasis.

The IRF2BP2 (IFN regulatory factor 2 binding protein 2) protein was identified as a nuclear protein that interacts with IFN regulatory factor 2 (IRF-2) and is an IRF-2-dependent transcriptional repressor. IRF2BP2 belongs to the IRF2BP family, which includes IRF2BP1, IRF2BP2, and IRF2BPL (EAP1). Recently, IRF2BP2 has emerged as an important new transcriptional cofactor in different biological systems, acting as a positive and negative regulator of gene expression. IRF2BP2 plays a role in different cellular functions, including apoptosis, survival, and cell differentiation. Additionally, IRF2BP2 may be involved in cancer development. Finally, it has been recently reported that IRF2BP2 may play a role in macrophage regulation and lymphocyte activation, highlighting its function in innate and adaptive immune responses. However, it has become increasingly clear that IRF2BP2 and its isoforms can have specific functions. In this review, we address the possible reasons for these distinct roles of IRF2BP2 and the partner proteins that interact with it. We also discuss the genes regulated by IRF2BP2 during the immune response and in other biological systems.