T-cell responses against rhinovirus species A and C in asthmatic and healthy children

Background Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic respiratory diseases. Infections by both species are prevalent in pre-school and school-aged children and, particularly for RV-C, can cause severe symptoms and a need for hospitalization. While associations between RV infection and asthma are well established, the adaptive immune-mechanisms by which RV infections influence asthma exacerbations are yet to be defined. Objective The aim of this study was to characterize and compare T-cell responses between RV-A and RV-C and to test the hypothesis that T-cell responses would differ between asthmatic children and healthy controls. Methods A multi-parameter flow cytometry assay was used to characterize the in vitro recall T-cell response against RV-A and RV-C in PBMCs from children with acute asthma (n = 22) and controls (n = 26). The responses were induced by pools of peptides containing species-specific VP1 epitopes of RV-A and RV-C. Results Regardless of children's clinical status, all children that responded to the in vitro stimulation (>90%) had a similar magnitude of CD4+ T-cell responses to RV-A and RV-C. However, asthmatic children had a significantly lower number of circulating regulatory T cells (Tregs), and healthy controls had significantly more Tregs induced by RV-A than RV-C. Conclusions and Clinical Relevance The comparable recall memory T-cell responses in asthmatic and control children to both RV-A and RV-C show that differences in the antibody and inflammatory responses previously described are likely to be due to regulation, with a demonstrated candidate being reduced regulatory T-cells. The reduced Treg numbers demonstrated here could explain the asthmatic's inability to appropriately control immunopathological responses to RV infections

Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C

Rhinovirus (RV) species A and C are the most frequent cause of respiratory viral illness worldwide and RV-C has been linked to more severe exacerbations of asthma in young children. Little is known about the immune response against the different RV species, although studies comparing IgG1 antibody titers found impaired antibody responses to RV-C. Therefore, the aim of this study was to assess whether T-cell immunity to RV-C is similarly impaired. We measured T-cell proliferation to overlapping synthetic peptides covering the entire VP1 capsid protein of an RV-A and RV-C genotype for 20 healthy adult donors. Human leukocyte antigen (HLA) was typed in all donors in order to investigate possible associations between HLA type and RV peptide recognition. Total and specific IgG1 antibody titers to VP1 of both RV-A and RV-C were also measured to examine associations between the antibody and T-cell responses. We identified T-cell epitopes that are specific of, and representative for each RV-A and RV-C species. These epitopes stimulated CD4+ specific T-cell proliferation with a similar magnitude of response for both RV species. All donors, independent of their HLA-DR or DQ type, were able to recognize the immunodominant RV-A and C regions of VP1. Furthermore, the presence or absence of specific antibody titers was not related with changes in T-cell recognition. Our results indicate a dissociation between the antibody and T-cell response against rhinoviruses. The species-representative T-cell epitopes identified in this study are valuable tools for future studies investigating T-cell responses to the different RV species