Rhinovirus (RV)-induced cell proliferation predicts response to experimental infection

Abstract

Rationale Because some patients with asthma develop severe respiratory symptoms during RV infections, we sought to identify baseline immune characteristics that would influence the course of an experimental RV16 infection in seronegative individuals. Methods PBMCs from 13 atopic asthmatic subjects and 6 normal subjects were incubated with RV16 or RV1A. Cell proliferation was determined ( 3H-thymidine), and IFNγ was measured in cell supernatants (ELISA). Subjects were then inoculated with RV16, symptoms assessed by daily questionnaire, and sputum and nasal lavage samples were collected at baseline and during infection. Results Baseline RV16-induced cell proliferation was closely correlated with RV1A-induced cell proliferation (r=0.83, p<0.001), and RV16-induced IFNγ (r=0.57, p=0.01). In contrast, RV16-induced cell proliferation was inversely related to cold symptom scores 2 days after inoculation(r=-0.59, p=0.01), and there was a similar, non-significant trend for RV16-induced IFNγ (r=-0.33, p=0.19). Higher RV16-induced PBMC proliferation was also associated with lower neutrophil counts in the nasal lavage one week after inoculation (r=-0.56, p=0.01) and with lower neutrophil counts in the sputum two weeks after inoculation (r=-0.52, p=0.03). Conclusions Subjects with higher RV-induced cell proliferation, likely representing a protective anti-viral response, have less severe inflammation and symptoms during infection. This suggests that protected individuals may have memory T cells that recognize RV16 and contribute to the antiviral response, even in the absence of RV16 neutralizing antibodies.