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

Abstract

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.

The two most clinically relevant rhinovirus species, RV-A and RV-C, stimulate similar recall CD4+ T cell responses in asthmatic and healthy children. However, the lower number of circulating regulatory T cells found for asthmatic children could contribute to their inability to control the immune response to rhinovirus infections, leading to pathological outcomes such as airway hyper-responsiveness commonly seen in exacerbations of asthma.