The Inversion of Naïve-to-Memory T Cell Ratios With Age: Potential Links to Autoimmunity and the Role of Lifetime Infection History

As individuals grow older, their T cell repertoire progressively shifts from being dominated by naïve T lymphocytes to featuring a preponderance of memory T cells. This phenomenon—well-documented in immunological literature—is frequently attributed to repeated antigenic stimulation over the course of a lifetime, coupled with thymic involution and other age-associated changes. Although memory T cells are crucial for rapid responses to previously encountered pathogens, there is increasing interest in whether this dramatically shifted balance might predispose certain individuals to a higher risk of autoimmunity, especially when compounded by chronic stress and recurrent infections. In this article, we propose a conceptual model linking the age-related inversion of the naïve-to-memory T cell ratio to an elevated likelihood of immune dysregulation. We integrate mathematical equations to capture the dynamic interactions among key variables, present simulated data in four informative graphs, and discuss the implications and limitations of our approach. Our goal is to invite a deeper consideration of how infection history, stress-induced immune breakdowns, and the intrinsic remodeling of T cell populations with age could collectively contribute to autoimmunity.