Differentiation and functions of CD8+ effector T cells

OBJECTIVE. Analyze Russian and foreign scientific literature reflecting the mechanisms of CD8⁺ Т -lymphocyte activation, lysis of infected cells, and the formation of possible immune dysfunctions.

MATERIALS AND METHODS. Recent Russian and international scientific literature from 1998 to 2025 on the biological features of CD8⁺ Т -lymphocyte activation was studied and analyzed. The primary sources were searched in the RINC, PubMed, Scopus, and Web of Science databases. The following combinations of keywords were used: T-lymphocyte subpopulations, cytotoxic T-lymphocytes, cytokines, granulins, perforin proteins, transcription factors, and hereditary mutations. A total of 49 articles were analyzed.

RESULTS. The differentiation of CD8⁺ Т cells depends on many factors, including CD4⁺ T lymphocytes, without which the formation of effector CD8+ T cells and memory T cells does not occur. Interleukins -2, -12, and IFN type I ensure the proliferation of CD8⁺ Т cells and their differentiation into cytotoxic lymphocytes. They stimulate the expression of transcription factors T-BET and BLIMP-1, which ensure the expression of perforin and granzymes. In chronic viral infections, T-cell differentiation is blocked by programmed cell death protein-1, as well as CTLA-4, TIM-3, LAG-3, and others. KIR receptors transmit inhibitory signals that prevent the destruction of uninfected cells by cytotoxic T lymphocytes. Thanks to the expression of NKG2D receptors, which recognize MHC-like class I molecules—MICA, MICB, and ULBP—that are expressed only by infected or transformed cells, “normal” cells and tissues are not damaged, activating nucleases in target cells. DISCUSSION. Cytotoxic T lymphocytes initiate the destruction of microbial DNA, as well as the genome of the target cell, thereby eliminating potentially infectious DNA. The functioning of cytotoxic T lymphocytes is affected by hereditary mutations associated with perforin and occurring in genes encoding proteins involved in exocytosis.

CONCLUSION. CD8⁺ Т lymphocytes proliferate and differentiate into CTLs containing cytotoxic granules, which enable them to lyse infected cells. Differentiation into CTLs is accompanied by the acquisition of mechanisms for destroying target cells and controlling various transcription factors. In the case of chronic antigen exposure (tumors, chronic viral infections), CD8⁺ Т cells initiate a response and begin to express inhibitory receptors that suppress the immune response.

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