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• W4327620698 endingPage "5662" @default.
• W4327620698 startingPage "5662" @default.
• W4327620698 abstract "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 tightly controlled by the PD-1/PD-L1 axis, thereby resembling the regulation of recalled memory T-cells of adults." @default.
• W4327620698 created "2023-03-17" @default.
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• W4327620698 date "2023-03-16" @default.
• W4327620698 modified "2023-10-18" @default.
• W4327620698 title "PD-1/PD-L1 Control of Antigen-Specifically Activated CD4 T-Cells of Neonates" @default.
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• W4327620698 doi "https://doi.org/10.3390/ijms24065662" @default.
• W4327620698 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36982735" @default.
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