Mayumi Saeki

Background: Human cytomegalovirus (CMV) is a major pathogen that poses significant risks to immunocompromised individuals and neonates. The tegument protein pp71, encoded by the UL82 gene, plays a pivotal role in initiating viral lytic replication and evading host immune responses. Despite its clinical relevance, standardized monoclonal antibodies (mAbs) for pp71 remain limited, prompting the need to expand the available repertoire of antibodies targeting this critical protein. Methods: In this study, we constructed a diverse human single-chain variable fragment (scFv) library using RNA derived from the B cells of four healthy donors. The library was expressed in Saccharomyces cerevisiae, and iterative rounds of magnetic-activated cell sorting (MACS) were performed against recombinant pp71. Clonal enrichment was monitored using flow cytometry. Results: Among the isolated clones, one designated ID2 exhibited high sensitivity and specificity for pp71, as demonstrated by flow cytometry, immunofluorescence, an enzyme-linked immunosorbent assay (ELISA), and biolayer interferometry (BLI). Conclusions: Collectively, these findings establish a novel pp71-specific mAb and underscore the utility of yeast surface display combined with MACS for expanding the antibody toolkit available for CMV research and diagnostics.

Bronchial asthma is a chronic disease characterized by reversible airway obstruction, mucus production, and bronchial hyperresponsiveness (BHR). Although Th2 cell-mediated eosinophilic inflammation is an important disease mechanism in the majority of patients with bronchial asthma, recent studies suggest the possible development of Th2-independent airway inflammation and BHR. These non-Th2 endotype patients seem to consist of multiple subgroups, and often do not respond to inhaled corticosteroids. Therefore, to understand the pathogenesis of asthma, it is important to characterize these non-Th2 subgroups. Recently, we demonstrated that Th9 cells induce eosinophil infiltration and eosinophil-independent BHR, and Th9 cells-mediated BHR may be resistant to glucocorticoid. In this review, we summarize the contribution of several T cell subsets in the development of bronchial asthma and introduce our recent study demonstrating Th9 cell-mediated and eosinophil-independent BHR.

Histamine, a prominent mediator of the symptoms and pathogenesis of allergic diseases, is produced not only by mast cells and basophils via the classical degranulation process but also by other immune cells including T cells via a neosynthesis process. Interestingly, T cells produce and are affected by histamine. Various T cell functions are also regulated by histamine via H1, H2, and H4 receptors. We recently demonstrated that T cells induce massive allergic inflammation without assistance from the immunoglobulin E (IgE)/mast cell-dependent pathway, and histamine may be involved in the development of allergic diseases via the functional modulation of and production by T cells. Based on these reports, we propose a new role of histamine and T cells in allergic diseases that differs from the established paradigm. Aside from our recent study showing the downregulation of regulatory T (Treg) cells by histamine via H1R and H4R in a murine allergic dermatitis model, the detailed roles of histamine and T cells in histamine production, expression of histamine receptors, and histamine-mediated activity for a series of T cell subsets remain to be elucidated.