Why and how does immunity
fade with age?
What can we do about it?

Older adults after the age of 50 years are more vulnerable to infections and infectious diseases. Age-related changes in immune cells, including T cells, contribute to this vulnerability. What is T cell aging? What mechanisms drive T cell dysfunction during aging? What are cell-intrinsic and environmental factors promoting poor T cell longevity and function? These are some of the questions we are asking to understand how different T cell subsets and antigen-specific T cells change during aging. The T cell compartment is exceptionally heterogenous with many T cell subsets (naive versus memory, CD4+ versus CD8+ versus gamma-delta T cells, MAIT, NKT, and many more subsets) that virtually all change with aging — but they age differently. We aim to determine the molecular mechanisms that contribute to T cell aging accounting for T cell heterogeneity, antigen-specificity, location in the body, and more.

Many vaccines fail to protect older adults adequately despite such vaccines being effective and durable in younger populations. To understand how protective T cell immunity can be restored we use varicella-zoster virus (VZV) vaccination as a clinically relevant model to contrast T cell memory responses across age groups and vaccine platforms. We found that, unlike CD8+ T cells, CD4+ are more resilient to aging and compensate for the defect in CD8+ memory T cells of older adults. Specifically, the Th17 phenotype of VZV-specific CD4+ cells confers durable protection in older adults despite aging defects. Maintaining Th17 functionality with aging could guide next-generation vaccine design tailored to older, vulnerable populations.

Senescent cells, permanently growth-arrested but bioactive, inflammatory signaling cells, accumulate with aging, drive diseases of aging and promote an inflammatory tone in tissues — inflammaging. How these cells are permitted to accumulate with aging despite being immunogenic remains elusive. We interrogate the communication between immune cells and senescent cells, immunosurveillance of senescent cells, and the contribution of immune aging to the accumulation and properties of senescent cells as well as the resultant tissue microenvironment.