Tanshinone I Enhances the Pulmonary Immune Response of CD8⁺ T Cells by Promoting Memory Differentiation

Objectives: Vaccination by a nonmucosal route to elicit CD8⁺ T cell-mediated mucosal immunity against respiratory infections presents a great challenge for the development of an effective vaccine or immunization strategy. This study aimed to explore a new strategy to address the challenge. Methods: To test this strategy, s.c. vaccinated mice were administered i.p. with tanshinone I (TSN1), a main bioactive compound found in the root of Salvia miltiorrhiza, and CD8⁺ T cell responses were analyzed using flow cytometry. The differentiating effects of TSN1 on CD8⁺ T cells from naïve mice were also evaluated in an in vitro setting. Results: Nonmucosal vaccination and administration of TSN1 induce pulmonary-resident vaccine-specific memory CD8⁺ T cells through increased lung-specific recruitment and retention. The improved memory response appears to result from the impact of TSN1 introduced during the primary immunization phase. Given a specific range of varying concentrations of this natural compound, it exhibits a differential effect on the memory differentiation of CD8⁺ T cells in the process of being activated. Effector memory T cells expand robustly relative to central memory T cells, and both memory subsets have additionally increased expression of CD44 and CD69. With more potent cytolytic activity, CD8⁺ Trm expressing CD69 particularly predominate the population lacking the CD69 expression in the lungs of TSN1-treated mice. Conclusions: Our study suggests that TSN1 as an important natural compound may hold great promise for novel approaches to the design and development of a more practical and efficient vaccination strategy to generate effective respiratory mucosal immunity.