Single-Cell Tracking Reveals a Role for Pre-Existing CCR5+ Memory Th1 Cells in the Control of Rhinovirus-A39 After Experimental Challenge in Humans

Abstract

We conclude that virus-specific CCR5+ effector memory CD4+ T cells primed by previous exposure to related viruses contribute to the control of rhinovirus.

T-bet+ Memory B Cells Link to Local Cross-Reactive IgG upon Human Rhinovirus Infection

“…Our findings echo earlier reports of B cell phenotypes capable of exerting effector function in tissues that were referred to as ''tissue-like'' based on molecular signatures that included the lack of CXCR5 (Ehrhardt et al, 2005;Lau et al, 2017;Li et al, 2016;Moir et al, 2008). A notable characteristic of dual-specific B cells was their expression of the Th1-associated chemokine receptors CCR5 and CXCR3, a feature shared with RV-specific Th1 effector memory cells (Muehling et al, 2016(Muehling et al, , 2018. Ligands for these receptors are induced by RV in nasal secretions and, thus, would be expected to aid in the coordinated recruitment of dual-specific B cells and Th1 cells to the site of infection (Muehling et al, 2018).…”

“…A notable characteristic of dual-specific B cells was their expression of the Th1-associated chemokine receptors CCR5 and CXCR3, a feature shared with RV-specific Th1 effector memory cells (Muehling et al, 2016(Muehling et al, , 2018. Ligands for these receptors are induced by RV in nasal secretions and, thus, would be expected to aid in the coordinated recruitment of dual-specific B cells and Th1 cells to the site of infection (Muehling et al, 2018). In accordance with this, the presence of dual-specific B cells in the nose during acute infection, coupled with the rapid production of cross-reactive IgG antibodies (but not IgA or IgM), supports an effector role for dualspecific B cells in the acute phase.…”

“…Next, to probe the possible functional relevance of a lack of CXCR5 expression on dual-specific B cells, we compared the phenotype of CXCR5À and CXCR5+ cells within total memory B cells. Those memory B cells that lacked CXCR5 were found to express higher levels of the transcription factor T-bet ($60% T-bet+), as well as the myeloid marker CD11c, and the Th1-associated receptors, CCR5 and CXCR3, whose ligands are induced in the nose during acute RV infection ( Figures 2I, 2J, and 2K) (Muehling et al, 2018). Moreover, CXCR5À memory B cells were enriched for the IgG isotype compared with their CXCR5+ counterpart ( Figure 2K).…”

“…Subjects were nasally inoculated with RV-A16 (300TCID 50 ) or RV-A39 (100 TCID 50 ) (Zambrano et al, 2003;Turner et al, 2017;Agrawal et al, 2014;Muehling et al, 2016Muehling et al, , 2018. Blood was drawn for isolation of PBMCs immediately before virus inoculation (baseline, day 0), during the acute infection phase (day 4 or 5), and at convalescence (day 21).…”

Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection, and cancer therapy

“…In the human rhinovirus challenge study yielding Dataset 1, MHC class II tetramers were used to identify rhinovirus-specific CD4 + T cells with the goal of tracking phenotypic changes over the course of infection. Increases in tetramer + cells on day 7 (Figure 2A) corresponded to the acute infection phase (Muehling et al, 2018). This tetramer tracking system for virus-specific T cells provided an opportunity to test whether the cells identified by T-REX were biologically significant by leaving the tetramer stain features out of the computational analysis (i.e., not using tetramers to make the UMAP or in other parts of T-REX) and then testing to see whether hotspots of cellular change identified by T-REX were statistically enriched for tetramer + , virus-specific cells.…”