Journal of Antivirals & Antiretrovirals
Open Access

Cytotoxic T Cells: Key Players in Viral Clearance

Patrice Fang^{* *}Correspondence: Patrice Fang, Department of Medicine, University of Peking, Beijing, China, Email:

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Description

As a vital part of the adaptive immune system, cytotoxic T cells, sometimes referred to as Cytotoxic T cells (CD8+) T cells, are essential for the removal of viral infections. These cells are distinguished by their ability to directly kill infected cells and are essential in maintaining cellular integrity and preventing the spread of pathogens. Their function and effectiveness in combating viral infections have been subjects of extensive research, providing insights into their mechanisms and applications in immunotherapy. During their maturation process, these cells undergo selection to ensure they can recognize foreign antigens presented by Major Histocompatibility Complex (MHC) class I molecules, while avoiding self-reactivity. The generation of functional T cells that can discriminate between healthy and infected cells depends on this selection process. The first signal is antigen-specific and occurs when the T Cell Receptor (TCR) binds to a peptide-MHC class I complex on the surface of an Antigen-Presenting Cell (APC). Once activated, cytotoxic T cells undergo differentiation into effector cells capable of executing their cytotoxic functions. Cytotoxic T lymphocytes can eliminate virus-infected cells in a variety of ways. Upon recognizing an infected cell, cytotoxic T cells release perforin, a protein that forms pores in the target cell membrane. Cytotoxic T cells also express Fas ligand, which binds to Fas receptors on the surface of target cells. This interaction triggers a cascade of events leading to apoptosis of the infected cell. Cytotoxic T cells produce cytokines such as Interferon-gamma (IFN-γ) and Tumor Necrosis Factor-alpha (TNF-α) that enhance the antiviral response. While TNF-α can directly cause death in target cells, IFN-γ improves antigen presentation by increasing the expression of MHC class I molecules.

Cytotoxic T cells are particularly effective against intracellular pathogens, including viruses, that replicate within host cells. They are instrumental in controlling and clearing viral infections such as influenza, Human Immunodeficiency Virus (HIV), hepatitis B and C, and cytomegalovirus. During influenza infections, cytotoxic T cells recognize and destroy virus-infected epithelial cells in the respiratory tract, reducing viral load and alleviating symptoms. In the case of HIV, cytotoxic T cells play a essential role in controlling viral replication by targeting and killing HIV-infected Clusters of differentiation 4 (CD4+) T cells. However, the virus has evolved mechanisms to evade these cells, complicating the immune response. In chronic hepatitis B and C infections, cytotoxic T cells contribute to liver damage by targeting infected hepatocytes. Despite their efforts, persistent viral infections can lead to immune exhaustion and liver disease. Despite their important role in viral clearance, cytotoxic T cells face several challenges. Many viruses have evolved mechanisms to evade detection by cytotoxic T cells. For example, some viruses downregulate MHC class I molecules on the surface of infected cells, reducing antigen presentation and making it harder for T cells to recognize and kill infected cells. During chronic viral infections, cytotoxic T cells can become exhausted, characterized by reduced functionality and persistence of the virus. This exhaustion is associated with the upregulation of inhibitory receptors and a decrease in effector functions. In some cases, the activity of cytotoxic T cells can contribute to tissue damage and tumorigenesis. This occurs when the immune response causes collateral damage to healthy cells or when the immune system mistakenly targets normal cells as if they were infected. Using cytotoxic T cells to their full extent could be therapeutic. Strategies such as adoptive T cell therapy and cancer vaccines aim to enhance the activity of cytotoxic T cells against viral infections and cancer. For example, Chimeric Antigen Receptor (CAR) T cell therapy involves engineering T cells to express receptors specific to tumor antigens, enabling them to target and kill cancer cells more effectively.

Conclusion

Cytotoxic T cells are indispensable in the immune system’s arsenal against viral infections, playing a central role in recognizing and eliminating infected cells. Their ability to induce apoptosis in target cells, produce antiviral cytokines, and contribute to long-term immunity underscores their importance in viral clearance. However, challenges such as viral evasion, immune exhaustion, and potential collateral damage highlight the complexity of their role. Advances in immunotherapy and vaccine development continue to build on our understanding of cytotoxic T cells, offering promising avenues for enhancing viral clearance and improving therapeutic outcomes. The ongoing research into cytotoxic T cells holds significant potential for advancing our ability to combat viral diseases and improve human health.