Human Th1 and Th2 Cells Targeting Rhinovirus and Allergen Coordinately Promote Allergic Asthma.

Abstract Background Asthmatic patients who are allergic are uniquely susceptible to acute wheezing episodes provoked by rhinovirus. However, the underlying immune mechanisms and interaction between RV and allergy remain enigmatic, and current paradigms are controversial. Objective To perform a comprehensive analysis of type 1 and type 2 innate and adaptive responses in allergic asthmatics infected with rhinovirus. Methods Circulating virus-specific Th1 cells and allergen-specific Th2 cells were precisely monitored before and after rhinovirus challenge in allergic asthmatics (total IgE 133–4692 IU/mL; n=28) and healthy non-allergic controls (n=12) using peptide/MHCII tetramers. T cells were sampled for up to 11 weeks to capture steady state and post-infection 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 asthmatics, higher numbers of circulating virus-specific PD-1+ Th1 cells, but not allergen-specific Th2 cells, were linked to worse lung function. Rhinovirus infection induced an amplified anti-viral Th1 response in asthmatics versus controls, with synchronized allergen-specific Th2 expansion, and production of type 1 and 2 cytokines in the nose. By contrast, Th2 responses were absent in infected asthmatics 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 Th1 cells and worse symptoms. Conclusions Rhinovirus induces robust Th1 responses in allergic asthmatics that may promote disease, even after infection resolves.