4.7 Review

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

Journal

EXPERIMENTAL AND MOLECULAR MEDICINE
Volume -, Issue -, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s12276-023-01105-x

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CD8 T cells play crucial roles in immune defense, and emerging evidence suggests the existence of distinct subsets with unique functions and therapeutic potential. Understanding these subsets is important for understanding immune responses in different diseases, and developing immunotherapeutic approaches targeting specific CD8 T-cell subsets holds great promise.
CD8 T cells play crucial roles in immune surveillance and defense against infections and cancer. After encountering antigenic stimulation, naive CD8 T cells differentiate and acquire effector functions, enabling them to eliminate infected or malignant cells. Traditionally, cytotoxic T cells, characterized by their ability to produce effector cytokines and release cytotoxic granules to directly kill target cells, have been recognized as the constituents of the predominant effector T-cell subset. However, emerging evidence suggests distinct subsets of effector CD8 T cells that each exhibit unique effector functions and therapeutic potential. This review highlights recent advancements in our understanding of CD8 T-cell subsets and the contributions of these cells to various disease pathologies. Understanding the diverse roles and functions of effector CD8 T-cell subsets is crucial to discern the complex dynamics of immune responses in different disease settings. Furthermore, the development of immunotherapeutic approaches that specifically target and regulate the function of distinct CD8 T-cell subsets holds great promise for precision medicine. In contrast to earlier beliefs that CD8 T cells primarily differentiate into cytotoxic T cells, recent advances have unveiled the presence of diverse subsets within the effector CD8 T cell population. Among these subsets, Tc17 cells have been extensively studied within the context of skin inflammation and the tumor microenvironment. Tc9 cells have shown links to specific autoimmune conditions alongside notable antitumor effects. Tfc cells, recognized for their role in supporting humoral responses, have also been identified within tumor microenvironments. Furthermore, regulatory CD8 T subsets have emerged in conditions such as graft-versus-host disease and autoimmune disorders, suggesting their potential contributions to immune modulation. These recent discoveries provide profound insights into the intricate landscape of immune regulation, offering promising avenues to harness or target these novel subsets for therapeutic interventions.

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