Functional and molecular hallmarks of CD8+ T cells. (IMAGE)
Caption
Functional and molecular hallmarks of CD8+T cells. (A) Functional effector CD8+ T cells. Functional effector CD8+ T cells express IFN-γ and TNF-α genes under transcriptional and epigenetic regulation. The cells have low inhibitor receptor expression (PD-1, LAG-3, TIGIT, TCR, and CTLA-4) and produce pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2), which amplify immune responses. Meanwhile, they exhibit efficient functional mitochondrial metabolism through mitochondrial mass and polarized mitochondria. These elements together ensure CD8+ T cells’ high proliferative ability and cytotoxicity for mounting immune responses. (B) Exhausted CD8+ T cells. Exhausted CD8+ T cells are characterized by pronounced expression of inhibitory receptors (PD-1, LAG-3, TIGIT, TCR, and CTLA-4) and diminished production of cytokines (IFN-γ, TNF-α, and IL-2). Exhausted CD8+ T cells exhibit mitochondrial dysfunction, accompanied by diminished mitochondrial mass and polarized mitochondria, and elevated ROS production. The cells show significantly elevated expression of exhaustion-associated genes (PDCD1 and TOX) under transcriptional and epigenetic regulation. Tox is required for exhausted CD8+ T cells’ epigenetic remodeling and survival. Exhausted CD8+ T cells display significantly diminished proliferative ability and cytotoxicity. CTLA-4, cytotoxic T-lymphocyte-associated protein 4; IL-2, interleukin-2; IFN-γ, interferon-gamma; LAG-3, lymphocyte activation gene 3; PD-1, programmed cell death protein 1; PDCD1, programmed cell death 1, also named PD-1; ROS, reactive oxygen species; TCR, T cell receptor; TIGIT, T cell immunoreceptors with Ig and ITIM domains; TNF-α, tumor necrosis factor alpha; TOX, thymocyte selection associated high mobility group box.
Credit
Cancer Biology & Medicine
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