TCR Repertoire Characterization for T Cells Expanded in Response to hRSV Infection in Mice Immunized with a Recombinant BCG Vaccine.

Emma Rey-Jurado,Alexis M Kalergis,Karen Bohmwald,Hernán G Correa

doi:10.3390/v12020233

Abstract

T cells play an essential role in the immune response against the human respiratory syncytial virus (hRSV). It has been described that both CD4+ and CD8+ T cells can contribute to the clearance of the virus during an infection. However, for some individuals, such an immune response can lead to an exacerbated and detrimental inflammatory response with high recruitment of neutrophils to the lungs. The receptor of most T cells is a heterodimer consisting of α and β chains (αβTCR) that upon antigen engagement induces the activation of these cells. The αβTCR molecule displays a broad sequence diversity that defines the T cell repertoire of an individual. In our laboratory, a recombinant Bacille Calmette–Guérin (BCG) vaccine expressing the nucleoprotein (N) of hRSV (rBCG-N-hRSV) was developed. Such a vaccine induces T cells with a Th1 polarized phenotype that promote the clearance of hRSV infection without causing inflammatory lung damage. Importantly, as part of this work, the T cell receptor (TCR) repertoire of T cells expanded after hRSV infection in naïve and rBCG-N-hRSV-immunized mice was characterized. A more diverse TCR repertoire was observed in the lungs from rBCG-N-hRSV-immunized as compared to unimmunized hRSV-infected mice, suggesting that vaccination with the recombinant rBCG-N-hRSV vaccine triggers the expansion of T cell populations that recognize more viral epitopes. Furthermore, differential expansion of certain TCRVβ chains was found for hRSV infection (TCRVβ+8.3 and TCRVβ+5.1,5.2) as compared to rBCG-N-hRSV vaccination (TCRVβ+11 and TCRVβ+12). Our findings contribute to better understanding the T cell response during hRSV infection, as well as the functioning of a vaccine that induces a protective T cell immunity against this virus.

Highlights

The human respiratory syncytial virus is a major cause of acute tract respiratory infections (ALRTI) in children and the elderly [1]
Cells (TCR+ CD69+ ) by flow cytometry (Figure 1E). Both mock-treated and human respiratory syncytial virus (hRSV)-infected cocultures showed a slight increase of CD69 expression after stimulation with heat-inactivated hRSV, indicating that the response was unspecific to the stimulus
These results unimmunized hRSV-infected mice was observed (Figure 5). These results suggest that rBCG-NrBCG-N-hRSV vaccination modified the T cell receptor (TCR) repertoire, which seemed diversified in the lungs, hRSV vaccination modified the TCR repertoire, which seemed diversified in the lungs, suggestingsuggesting an increased capacity to respond to atolarger number

Summary

Introduction

The human respiratory syncytial virus (hRSV) is a major cause of acute tract respiratory infections (ALRTI) in children and the elderly [1]. Infection with hRSV produces pulmonary inflammatory hyperresponsiveness with significant lung damage due to a T helper 2 (Th2)-biased immune response in the susceptible [2]. Along these lines, elevated Th2 cytokines including IL-3, IL-4, IL-10 and IL-13 were found in the airways in infants with hRSV bronchiolitis [3]. Upon hRSV infection in mice, moderate bronchiolitis, reduced activity and weight loss is observed [4,5]. HRSV-associated immunopathology can be measured by body weight loss and infiltration of neutrophils into the lungs [6]. CD4+ and CD8+ T cells are important for the immune response against hRSV infection [7]. Several vaccine approaches have been evaluated, up to date, no licensed

Methods

Results

Conclusion