Human T_H1 and T_H2 cells targeting rhinovirus and allergen coordinately promote allergic asthma.

ABSTRACT:

Background

Allergic asthmatic subjects are uniquely susceptible to acute wheezing episodes provoked by rhinovirus. However, the underlying immune mechanisms and interaction between rhinovirus and allergy remain enigmatic, and current paradigms are controversial.

Objective

We sought to perform a comprehensive analysis of type 1 and type 2 innate and adaptive responses in allergic asthmatic subjects infected with rhinovirus.

Methods

Circulating virus-specific T_H1 cells and allergen-specific T_H2 cells were precisely monitored before and after rhinovirus challenge in allergic asthmatic subjects (total IgE, 133-4692 IU/mL; n = 28) and healthy nonallergic controls (n = 12) using peptide/MHCII tetramers. T cells were sampled for up to 11 weeks to capture steady-state and postinfection phases. T-cell responses were analyzed in parallel with 18 cytokines in the nose, upper and lower airway symptoms, and lung function. The influence of in vivo IgE blockade was also examined.

Results

In uninfected asthmatic subjects, higher numbers of circulating virus-specific PD-1⁺ T_H1 cells, but not allergen-specific T_H2 cells, were linked to worse lung function. Rhinovirus infection induced an amplified antiviral T_H1 response in asthmatic subjects versus controls, with synchronized allergen-specific T_H2 expansion, and production of type 1 and 2 cytokines in the nose. In contrast, T_H2 responses were absent in infected asthmatic subjects who had normal lung function, and in those receiving anti-IgE. Across all subjects, early induction of a minimal set of nasal cytokines that discriminated high responders (G-CSF, IFN-γ, TNF-α) correlated with both egress of circulating virus-specific T_H1 cells and worse symptoms.

Conclusions

Rhinovirus induces robust T_H1 responses in allergic asthmatic subjects that may promote disease, even after the infection resolves.

SUBMITTER: Muehling LM 

PROVIDER: S-EPMC7483727 | biostudies-literature |

REPOSITORIES: biostudies-literature