Assistant Professor University of Rochester School of Medicine and Dentistry Rochester, New York, United States
Background: Allergic airway diseases, including allergic rhinitis and asthma are highly prevalent. Respiratory viruses are known triggers of allergic airway exacerbations with IgE-mediated modulation of antiviral responses as one mechanism underlying this link. Innate immune cells, such as monocytes and dendritic cells, are critical for antiviral responses and T cell activation, however, in allergic disease, these functions are altered. Interestingly, during the SARS-CoV-2 pandemic, some studies suggested atopic disease was associated with 1) less severe infection and 2) development of post-COVID conditions, indicating atopy may influence SARS-CoV-2 pathogenesis. Objective: Determine if IgE-mediated innate immune cell phenotypes are associated with differential SARS-CoV-2 specific CD4 T cell responses in children and adults. Design/Methods: Children (n=11) and adults (n=13) were recruited from April 2022-July 2023. Adults had received a recommended SARS-CoV-2 vaccine series. All children had received a 3-dose series of Pfizer/BioNTech vaccine. Most had known prior SARS-CoV-2 infection/exposure. PBMCs were evaluated for 1) innate cell phenotypes via spectral flow cytometry, or 2) stimulated with SARS-CoV-2 peptides followed by flow cytometry for activation induced markers and intracellular cytokines to measure virus-specific CD4 memory T cell responses. Serum IgE levels were determined. Results: Monocytes and dendritic cell subsets had differential expression of surface IgE and the high affinity IgE receptor, FceRI, correlating with serum IgE levels. There was no difference in serum IgE levels or IgE receptor expression between adults and children. Both children and adults produced polyfunctional SARS-CoV-2-specific CD4 T cells with differences across age. Analysis of innate cell phenotypes, showed that monocyte surface IgE and IgE receptor expression correlated with SARS-CoV-2 specific IFNg+ CD4 T cells. IL-4 and IL-17 expressing cells were identified but in preliminary analysis, these subsets did not correlate with IgE-related phenotypes.
Conclusion(s): Both adults and children make polyfunctional SARS-CoV-2 antiviral CD4 T cells. This data suggests that IgE-induced phenotypic changes in innate antigen presenting cells, such as monocytes, influences SARS-CoV-2 specific CD4 T cell phenotypes and responses. This is further evidence that allergic inflammation alters antiviral responses in vivo. While significant differences were not observed between adults and children in this small cohort, larger future studies will elucidate the intersection of age and atopy in regulating virus-specific T cell responses.
