Age-Stratified Treg Responses During Viral Infections of the Central Nervous System: A Literature Review

Abstract

Regulatory T cells (Tregs) play a vital role in limiting inflammation and resolving the immune response after a viral infection. Within the central nervous system (CNS), Tregs are especially important for the protection of neurons, which have limited regenerative capacity, and the preservation of myelin sheaths, which support neuronal function and survival. Nevertheless, viral infections of the CNS often result in enduring neurological dysfunction, especially in more vulnerable age groups such as newborns and the elderly. Although it is appreciated that Treg activity changes with age, it is unclear how these age-dependent changes impact viral CNS infections. In this review, we explore Treg development over the life of the host and discuss evidence for age-dependent Treg responses to peripheral viral infections. We also discuss the CNS-specific roles of Tregs, where both immunomodulatory and neuroprotective functions can contribute to preservation of brain cells. Finally, we examine the current evidence for Treg activity in neurotropic infections in the context of age, and highlight gaps in our understanding of Treg function in younger and older hosts. Overall, a better understanding of age-dependent Treg activity in the CNS may reveal opportunities for therapeutic interventions tailored to the most vulnerable ages.