Regulation of antiviral immunity by PD-1 during respiratory syncitial virus infection and upon vaccination.

Respiratory syncytial virus (RSV) induces a protective immune response shaped by regulatory pathways that control T cell function. The inhibitory receptor PD-1 is a central modulator of these processes. Here, we analyzed PD-1, LAG-3, and TIM-3 expression in CD8+ T cells during RSV infection and evaluated PD-1/PD-L1 modulation across different immunological contexts in mice. PD-1 expression progressively increased in lung CD8+ T cells at 5- and 9-day post-infection, accompanied by co-expression of LAG-3 and TIM-3, and elevated PD-L1 in epithelial and antigen-presenting cells. PD-1 modulation varied with context: passive immunization reduced its expression, whereas rBCG-N-RSV vaccination followed by infection increased PD-1 and cytokine production. PD-1 blockade enhanced memory T cell generation and the quality of the humoral response, whereas PD-1 deficiency impaired these responses. These findings support a context-dependent role for PD-1 in coordinating antiviral immunity and vaccine-induced immune responses.