The role of epigenetics in the acquisition and maintenance of effector function in virus‐specific CD8 T cells

Abstract

SummaryCD8 1 T cells are critical for protecting the body from infectious disease. To achieve this protection, CD81 T cells must undergo a highly involved process of differentiation that involves the activation of naïve/quiescent cells followed by robust rounds of cell division and the acquisition of effector functions that mediate viral clearance. After the pathogen is eliminated, a small number of these cells survive into long-lived memory and maintain the capacity to respond rapidly and reacquire effector function after secondary exposure to their cognate antigen. This review focuses on how CD81 T cells acquire and regulate effector functions and how the capacity to produce effector molecules is maintained into memory. IUBMBIUBMB Life, 62(7): [519][520][521][522][523][524][525][526] 2010

Interferon Regulatory Factor 4 Sustains CD8+ T Cell Expansion and Effector Differentiation

“…To this end, we observed diminished binding by T-bet to the Gzmb and Ifng promoters in IRF4-deficient CD8 + T cells (Figure 6 I), suggesting that IRF4 is required for the function of T-bet. The effector differentiation of CD8 + T cells is accompanied by intensive epigenetic chromatin modifications in the promoter regions of effector molecule genes (Olson et al, 2010). These active chromatin modifications are required for effector molecule expression and lineage specification of effector CD8 + T cells.…”

Maintenance of CMV-specific CD8+ T cell responses and the relationship of IL-27 to IFN-γ levels with aging

“…In the current study, we investigated whether young and elderly people infected with CMV had similar levels of CD8 + T cell cytokine production and proliferation in response to a immunodominant CMV pp65 peptide pool given the role of CD8 + T cells in controlling viral infection and the association of CMV with immunosenescence [1, 30, 31]. In addition, we determined the effects of aging and CMV-infectious status on plasma levels of IL-27 as well as on its relationship to IFN-γ in that IL-27 can promote the production of IFN-γ [16].…”

“…CD8 + T cells are critically involved in host defense against viral infections [1]. These cells can directly kill virus-infected cells.…”

“…Cytomegalovirus (CMV), which establishes persistent infection, has been suggested as a potential driving force for the age-associated expansion of memory CD8 + T cells based on the observations showing the increased frequency of CMV-specific cells in the expanded memory CD8 + T cells [8–10]. CD8 + T cells, a major cellular source of IFN-γ, are critically involved in defending the host against viral infection and reactivation [1]. These findings suggest a possible change in cytokine production and proliferation of CMV-specific CD8 + T cells in humans with aging, leading to the altered proportion of CMV-specific CD8 + T cells.…”

Time-dependent alterations in memory CD8 T cell function after infection

“…The granule exocytosis pathway constitutes another mode of CD8 T cell-mediated killing, in which perforin facilitates the delivery of cytolytic granzyme molecules to infected cells, initiating apoptosis of target cells [28][29][30]. Activation of CD8 T cells also results in the production and release of cytokines including IFN-γ, TNF-α, and IL-2 that stimulate the microbicidal activity of innate immune cells, lead to increased expression of major histocompatibility complex (MHC) I on target cells, and can act upon adaptive immune cells to regulate adaptive immune responses [7,[31][32][33][34]. CD8 T cells can also produce chemokines including RANTES, MIP-1α, and MIP-1β that aid in the recruitment of immune cells to sites of infection [35].…”