Publications by authors named "P L Schwartzberg"
We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity.
View Article and Find Full Text PDFDevelopment of protective immune responses relies on a balance between proinflammatory CD4 T helper (Th) cell populations such as Th17 cells and regulatory CD4 T cells (Tregs) that keep immune activation in check. Evidence that interleukin-2-inducible T cell kinase (Itk) regulates this balance supports therapeutic applications for Itk inhibition.
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- The study examines how the adjuvant AS03 affects vaccination responses in humans receiving the H5N1 influenza vaccine by analyzing data over 14 time points, including the immediate aftermath of the vaccination.
- Researchers developed a computational method to identify complex immune response patterns, revealing differences in how the immune system responds to the vaccine with and without the adjuvant at different stages of vaccination (prime and boost).
- Findings indicate that certain immune response signatures persist long after vaccination, and specific immune cell characteristics, particularly in monocytes and CD8 T cells, are associated with stronger antibody responses, suggesting that pre-existing immune states can influence vaccine effectiveness.
Article Synopsis
- The study identifies a new pair of transcription factors, Bhlhe40 and Pou2af1, that regulates CXCR5 expression, which is crucial for follicular T helper (Tfh) cell migration into germinal centers.
- Pou2af1 promotes Tfh formation and migration by increasing CXCR5 levels, while Bhlhe40 inhibits this by repressing Pou2af1 expression.
- The research suggests that the Bhlhe40-Pou2af1 regulatory circuit operates independently of the well-established Bcl6-Blimp1 circuit that traditionally governs Tfh cell fate.
Effective high-affinity, long-term humoral immunity requires T cell help provided by a subset of differentiated CD4 T cells known as T follicular helper (Tfh) cells. Classically, Tfh cells provide contact-dependent help for the generation of germinal centers (GCs) in secondary lymphoid organs (SLOs). Recent studies have expanded the conventional definition of Tfh cells, revealing new functions, new descriptions of Tfh subsets, new factors regulating Tfh differentiation, and new roles outside of SLO GCs.
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