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

Cibele M Gaido; Caitlyn Granland; Ingrid A Laing; Peter N Le Souëf; Wayne R Thomas; Andrew J Currie; Belinda J Hales

doi:10.1002/iid3.206

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

Immun Inflamm Dis. 2018 Mar;6(1):143-153. doi: 10.1002/iid3.206. Epub 2017 Nov 10.

Authors

Cibele M Gaido^{1

2}, Caitlyn Granland^{1

2}, Ingrid A Laing^{1

2}, Peter N Le Souëf^{2

3}, Wayne R Thomas¹, Andrew J Currie^{2

4}, Belinda J Hales¹

Affiliations

¹ Telethon Kids Institute, The University of Western Australia, Perth, Australia.
² School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia.
³ Princess Margaret Hospital for Children, Perth, Australia.
⁴ School of Veterinary & Life Sciences, Murdoch University, Perth, Australia.

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.

Keywords: Asthma; T-cell proliferation; regulatory T-cells; rhinovirus.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Asthma* / immunology
Asthma* / pathology
Asthma* / virology
Child
Child, Preschool
Coxsackievirus Infections* / immunology
Coxsackievirus Infections* / pathology
Coxsackievirus Infections* / virology
Enterovirus / immunology*
Female
Humans
Immunologic Memory*
Infant
Male
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / pathology

Supplementary concepts

Rhinovirus A
Rhinovirus B