Fig. 1.

The life cycle of CD8⁺ T cells. (A) Birth of mature CD8⁺ T cells. Red bone marrow produces pre-T cells, which are recruited to the thymus under the action of chemokines. Subsequently, T cells undergo positive and negative selection to become mature CD4⁺T or CD8⁺T cells, assisted by antigen-presenting cells (APCs), thymic epithelial cells and thymic factors. (B) Activation of CD8⁺ T cells. The activation of CD8⁺ T cells requires the assistance of three signals, namely the precursor signal triggered by the binding of TCR and MHC-I, the ligand mediated co-stimulatory signal and the supplementary signal produced by cytokines. ITAM, immunoreceptor tyrosine-based activation motif; LCK, lymphocyte-specific protein tyrosine kinase. (C) Anti-tumor effect of CD8⁺ T cells. CD8⁺ T cells can form immune synapses with target cells after activation. Subsequently, CD8⁺ T cells release granzymes, perforin, and cytokines to destroy tumor cells. Meanwhile, CD8⁺ T cells express the death receptor Fas-L and induce apoptosis in Fas expressing tumor cells. In addition, activated CD8⁺ T cells may kill target cells through the delivery of EVs. Tumor antigens, once released, are presented by DCs and T cells are activated to infiltrate tumors, recognizing and dismantling tumor cells. LFA-1, lymphocyte function-associated antigen 1; ICAM, intercellular cell adhesion molecule. (D) The fate of CD8⁺ T cells. CD8⁺ T cells expressing death ligand receptors can induce activated cell death of their own or adjacent CD8⁺ T lymphocytes. Meanwhile, apoptosis related gene 2 can accelerate the CD8⁺ T cell death by cleaving the differentiation protein of myeloid leukemia cells. The expression of pro-apoptotic proteins BAX and BAK enhances mitochondrial membrane permeability, leading to the activation of cytochrome c and its binding to apoptotic protease activating factor-1, further leading to caspase 8/-3 dependent cell death