The role of regulatory T cells in infant HIV pathogenesis: therapeutic strategies.

Regulatory T cells (Tregs) are pivotal in maintaining immune homeostasis by suppressing excessive immune responses, thereby preventing immunopathology. In the context of infant human immunodeficiency virus (HIV) infection, Tregs exhibit a dualistic role: while they mitigate immune activation, they may also impede effective antiviral immunity, facilitating viral persistence. Recent studies have illuminated the nuanced involvement of Tregs in infant HIV pathogenesis. For instance, research has demonstrated that HIV-exposed uninfected infants exhibit lower frequencies of peripheral blood Tregs at birth compared to unexposed infants, leading to a delayed expansion of these cells over the first 36 weeks of life. This disruption in Treg development is associated with gut epithelial damage, suggesting that compromised mucosal integrity may influence Treg dynamics in early life. Tregs influence HIV pathogenesis in infants through several mechanisms. They suppress the activation and proliferation of effector T cells, including HIV-specific CD8+ cytotoxic T lymphocytes, which are crucial for controlling viral replication. This suppression can lead to inadequate immune responses against HIV, allowing the virus to persist and replicate. Additionally, Tregs can modulate the function of dendritic cells, leading to suboptimal antigen presentation and further dampening the adaptive immune response. Moreover, an imbalance between Tregs and Th17 cells, another subset of CD4+ T cells involved in mucosal immunity, has been observed in HIV-infected individuals. The loss of Th17 cells, coupled with an increase in Tregs, can compromise mucosal barriers, facilitating microbial translocation and chronic immune activation, which are hallmarks of HIV disease progression.