PD-1/PD-L1 Control of Antigen-Specifically Activated CD4 T-Cells of Neonates

作者：Christiane Majer, Holger Lingel, Aditya Arra, Hans‐Gert Heuft, Dirk Bretschneider, Silke Balk, Katrin Vogel, Monika Christine Brunner-Weinzierl · 发表于：International Journal of Molecular Sciences · 年份：2023 · DOI：10.3390/ijms24065662 · 被引用次数：8 · 研究领域：Pneumonia and Respiratory Infections、COVID-19 Impact on Reproduction、Neonatal Health and Biochemistry

Newborns are highly susceptible to infections; however, the underlying mechanisms that regulate the anti-microbial T-helper cells shortly after birth remain incompletely understood. To address neonatal antigen-specific human T-cell responses against bacteria, Staphylococcus aureus (S. aureus) was used as a model pathogen and comparatively analyzed in terms of the polyclonal staphylococcal enterotoxin B (SEB) superantigen responses. Here, we report that neonatal CD4 T-cells perform activation-induced events upon S. aureus/APC-encounter including the expression of CD40L and PD-1, as well as the production of Th1 cytokines, concomitant to T-cell proliferation. The application of a multiple regression analysis revealed that the proliferation of neonatal T-helper cells was determined by sex, IL-2 receptor expression and the impact of the PD-1/PD-L1 blockade. Indeed, the treatment of S. aureus-activated neonatal T-helper cells with PD-1 and PD-L1 blocking antibodies revealed the specific regulation of the immediate neonatal T-cell responses with respect to the proliferation and frequencies of IFNγ producers, which resembled in part the response of adults’ memory T-cells. Intriguingly, the generation of multifunctional T-helper cells was regulated by the PD-1/PD-L1 axis exclusively in the neonatal CD4 T-cell lineage. Together, albeit missing memory T-cells in neonates, their unexperienced CD4 T-cells are well adapted to mount immediate and strong anti-bacterial responses that are ti...