γδ T Cells in Aging

Among immune cells, γδ T cells garner increasing attention in the context of aging, attributed to their unique functionality in maintaining homeostasis and potential therapeutic implications. Creative Biolabs explores the distinct dynamics and characteristics of γδ T cells during aging and potential strategies for γδ T cell-related immunotherapies.

γδ T Cells in Aging

Aging is intrinsically linked with a systemic metamorphosis of the immune system, leading to immunosenescence, a state marked by declining immunity and altered functionality of various immune cells, including γδ T cells. Notwithstanding the scanty proportion, γδ T cells have a substantial impact on immune responses, especially during aging.

• Expansion and Functionality
  The most striking characteristic of γδ T cells during aging is their marked clonal expansion. Multiple studies have indicated an increasing proportion of γδ T cells with age, specifically the Vγ9Vδ2 subset in the peripheral blood.
• Immunosenescence
• Aging is known to induce notable changes in γδ T cell phenotype, characterized by an increased expression of NK cell receptors like NKG2D, CD16, and CD57 and a high production of cytomegalovirus (CMV)-specific T cells.
• Elevated chronological age is associated with a reduction in telomere length and telomerase activity in γδ T cells, indicative of cellular senescence.

Fig.1 Developmental waves of human γδ T cells.¹

The Role of γδ T Cells in Age-related Diseases

Compelling evidence has portrayed γδ T cells as a key player in multiple age-related diseases, particularly cancer and autoimmune disorders, emphasizing their immense therapeutic potential.

• The cytotoxic activity of Vγ9Vδ2 T cells, mediated primarily through the recognition of phosphor-antigens, aids in the eradication of multiple types of tumors. Nonetheless, cancer patients often exhibit an impaired γδ T cell function and lack of response towards phosphor-antigens, which can be potentially harnessed for therapeutic interventions.
• Rheumatoid arthritis, a common autoimmune disorder, witnesses an upregulation of γδ T cells in the inflamed synovial tissue, suggesting their potential involvement in local inflammation and tissue damage.

Therapeutic Implications of γδ T Cells

Efforts to exploit the therapeutic potential of γδ T cells in the context of aging primarily revolve around two strategies: enhancing γδ T cell anti-tumor activity and restraining γδ T cell pro-inflammatory responses.

• Strategies aimed at bolstering the anti-tumor activity of γδ T cells include the use of amino bisphosphonates and synthetic phosphor-antigens to trigger Vγ9Vδ2 T cell proliferation and activation.
• Therapeutic interventions could include inhibitors dampening γδ T cell-activated signaling pathways or reducing the expression of co-stimulatory molecules to alleviate their pro-inflammatory responses.

The multifaceted role of γδ T cells in aging undeniably engages a broad spectrum of alterations and implications that encompass immune senescence, age-related diseases, and potential therapeutic strategies. It is, therefore, essential to further decipher the complexity of the γδ T cell aging process to formulate innovative interventions.

Creative Biolabs is committed to advancing our understanding of γδ T cells and their applications.

Reference

1. Fichtner, Alina Suzann, Sarina Ravens, and Immo Prinz. "Human γδ TCR repertoires in health and disease." Cells 9.4 (2020): 800.