T-Cell Co-Signaling in Normal Human Ageing – A Silver Bullet for Ageing?

Introduction

Even in “healthy” ageing, the immune system undergoes significant changes, with these immune system aberrations being collectively known as immunosenescence. These changes are complex, occurring both in the innate and the adaptive immune system, though recent focus has been on changes in the adaptive immune system due to increasing availability of highly targeted immunomodulatory drugs coming into clinical use. Managing immunosenescence is important for older adults as these immune changes contribute to their increased susceptibility to infections, poor response to vaccines, weakened cancer immunosurveillance and increased risk of autoimmune disease.

This narrative review considers the underlying mechanisms of T-cell co-signaling changes, as a potential modifiable target in immunosenescence.

Method

Structured searches of Medline OVID, SCOPUS, Web of Science and PubMed were performed with MeSH terms relating to ageing, T-cell co-signaling and therapeutic interventions. Duplicates were removed, abstracts screened, and papers organised thematically.

Results

The literature highlights a general decrease in excitatory signaling, with a concurrent increase inhibitory signaling, in T-cells in healthy ageing. This leads to lower proliferative capacity of T-cells in response to a novel antigen and thus a less competent immune response. Potential interventions to overcome these changes exist, spanning from lifestyle interventions such as horticultural therapy, to use of monoclonal antibody therapies to directly modulate immune responses.

Conclusions

T-cells have worsening function with age, in part due to weakened excitatory cos-signaling and strengthened co-inhibitory signaling. There is potential for these changes to be modified with novel medical therapies to overcome age-relate immune changes.