CD8+ T cell exhaustion

• Published in: Seminars in immunopathology Vol. 41; no. 3; pp. 327 - 337
• Main Author: Kurachi, Makoto
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2019; Springer Nature B.V
• Subjects: Animals; Antigens - immunology; Biomedical and Life Sciences; Biomedicine; Cancer; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Chronic infection; Disease Susceptibility - immunology; Effector cells; Gene Expression Regulation; Humans; Immunological memory; Immunology; Immunomodulation; Inflammation; Internal Medicine; Lymphocytes; Lymphocytes T; Memory cells; PD-1 protein; Receptor mechanisms; Review; Signal Transduction; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Transcription; CD8 T cell; Chronic infection; Cancer immunotherapy; Exhaustion; Inhibitory receptor
• ISSN: 1863-2297; 1863-2300; 1863-2300
• DOI: 10.1007/s00281-019-00744-5

CD8 + T cells are important for the protective immunity against intracellular pathogens and tumor. In the case of chronic infection or cancer, CD8 + T cells are exposed to persistent antigen and/or inflammatory signals. This excessive amount of signals often leads CD8 + T cells to gradual deterioration of T cell function, a state called “exhaustion.” Exhausted T cells are characterized by progressive loss of effector functions (cytokine production and killing function), expression of multiple inhibitory receptors (such as PD-1 and LAG3), dysregulated metabolism, poor memory recall response, and homeostatic proliferation. These altered functions are closely related with altered transcriptional program and epigenetic landscape that clearly distinguish exhausted T cells from normal effector and memory T cells. T cell exhaustion is often associated with inefficient control of persisting infections and cancers, but re-invigoration of exhausted T cells with inhibitory receptor blockade can promote improved immunity and disease outcome. Accumulating evidences support the therapeutic potential of targeting exhausted T cells. However, exhausted T cells comprise heterogenous cell population with distinct responsiveness to intervention. Understanding molecular mechanism of T cell exhaustion is essential to establish rational immunotherapeutic interventions.