Cytotoxic T cells, also called CD8+ T cells, are immune lymphocytes that recognize antigens presented on major histocompatibility complex class I molecules and destroy infected or malignant cells using cytolytic molecules.
Explanation and context
Cells of the adaptive immune system coordinate elimination of pathogens and abnormal cells. Cytotoxic T cells (CTLs) arise when naive CD8+ T lymphocytes encounter antigenic peptides displayed by MHC class I molecules on antigen-presenting cells. Engagement of the T-cell receptor, along with co-stimulation and cytokines like interleukin-2, triggers clonal expansion and differentiation into effector CTLs. Mature CTLs patrol tissues, inspecting cells for foreign or altered peptides displayed on MHC I. When a target is recognized, the CTL forms an immunological synapse and releases perforin and granzymes from cytotoxic granules, inducing apoptosis in the target cell. CTLs also express Fas ligand, which can engage the Fas receptor on target cells to initiate programmed cell death. This mechanism is central to clearing virus-infected cells, intracellular bacteria and protozoa, and cells undergoing malignant transformation. CTLs contribute to transplant rejection by recognizing mismatched MHC class I molecules on graft tissues. Memory CD8+ T cells persist after an infection, providing long-term protection by rapidly responding upon re-exposure to the same pathogen. CTLs require assistance from CD4+ helper T cells for optimal activation and maintenance. Dysregulation of CTL responses can lead to immunopathology, as seen in chronic viral infections and some autoimmune diseases. Understanding CTL biology has guided therapeutic approaches, such as adoptive cell transfer and vaccination strategies aiming to elicit strong CD8+ responses.
Key roles and examples
Influenza-specific cytotoxic T cells clear infected respiratory epithelial cells and contribute to recovery from infection. CTLs targeting HIV are a major force in controlling viral replication, though HIV can evade complete clearance. Transplanted organs are rejected when recipient CTLs recognize donor MHC class I molecules as foreign. Cancer immunotherapies like chimeric antigen receptor (CAR) T-cell therapy reprogram patient T cells to recognize tumor antigens and exploit CTL killing mechanisms. Some viruses downregulate MHC I expression or inhibit antigen processing to escape CTL detection, underscoring the ongoing evolutionary arms race between pathogens and host immunity.
Cytotoxic T cells are essential defenders against intracellular pathogens and transformed cells. By understanding how they develop and function, researchers can design vaccines and therapies that harness their destructive capabilities while avoiding excessive tissue damage.
Related Terms: CD8+ T cell, Helper T cell, Major histocompatibility complex, Perforin, Granzymes