Multiple Functions of γδ T Cells in the Progression of Viral Infections

Advanced discoveries in the field of immunology have partially unraveled the mysteries of the immune system. Among the unsung heroes protecting an organism from a variety of infections, γδ T cells have turned out to be a unique arm of the immune response. Their roles in anti-microbial defenses, epitomized by γδ T cell engagement in viral host defenses, are just beginning to be fully understood.

Fig. 1 Functions of mouse or human γδ T cells and their subsets in inhibiting or promoting the pathogenesis of HBV or HCV infection.¹

Here, Creative Biolabs discusses the multi-functional involvement of γδ T cells in the progression of viral infections.

Multiple Functions of γδ T Cells in Viral Infections

Studies have identified a prolific enhancement in the number of γδ T cells during a variety of viral infections, pointing to their pivotal role in viral host defenses. Whether it's Hepatitis virus, Influenza virus, HIV, or Cytomegalovirus (CMV), these cells dynamically respond and adjust according to the type, phase, and localization of the infection, thereby acting in a tailored manner to prevent an infected cell from wreaking havoc in the body.

• Phospho-antigen recognition
• APC engagement
• Enhancement of Natural Killer (NK) cell functions through co-stimulation
• Cytotoxic properties

Different γδ T-cell subsets, predominantly Vγ9/Vδ2 and Vδ1 T cells, display differential function and tissue distribution in response to viral infections.

Vγ9/Vδ2 T Cells in Viral Infections

Vγ9/Vδ2 cells make up the majority of γδ T cells in the peripheral blood and are extensively studied for their role in combating viral infections.

• Their primary function involves sensing the accumulation of phosphor-antigens, a metabolic byproduct of infectious pathogens within infected cells, kick-starting a rapid and potent antimicrobial response.
• These cells can also serve as professional antigen-presenting cells (APCs), fostering a link between the innate and adaptive response during early viral infection. As APCs, γδ T cells can process and present viral antigens to αβ T cells, inducing their activation and differentiation, thereby amplifying the immune response.

Vδ1 T Cells in Viral Infections

In contrast, Vδ1 T cells, predominantly found in epithelial tissues such as the skin, gut, and lung, exhibit a more subtle, steady state anti-viral role as tissue-resident lymphocytes.

• They recognize stress-induced molecules on virus-infected cells, such as MICA/B, ULBPs, CD1d, which are upregulated during infections and cellular distress, hence playing a crucial role in the innate immune response.
• In respiratory viral infections like Influenza, which majorly exhibit cytopathology in lung epithelium, Vδ1 T cells contribute significantly to tissue repair and immune regulation.

γδ T Cells May Harbor a Dark Side in Viral Infections

Despite these numerous anti-viral defense mechanisms, γδ T cells may also harbor a dark side in viral infections. Studies on HIV infections have reported the potential role of Vδ2 cells as reservoirs for the virus, leading to concerns about their exploitation by certain viruses for survival and propagation.

At Creative Biolabs, we continue to pioneer research on γδ T cells. We aim for a thorough understanding of these unique cells and their role in viral infections, unraveling their full potential for therapeutic applications.

Reference

1. Hou Wen and Xiaoli Wu. "Diverse functions of γδ T cells in the progression of hepatitis B virus and hepatitis C virus infection." Frontiers in Immunology 11 (2021): 619872.