Monitoring Circulating Virus-Specific CD4+ T Cells and Probiotic Effect in an Experimental Rhinovirus Challenge Model
Saturday, March 5, 2016: 2:00 PM
Room 406AB (Convention Center)
Lyndsey M. Muehling, MS, , , , , , , ,
Rationale: Rhinovirus (RV) is a major cause of common cold and an important trigger of asthma exacerbations. T-cell responses to RV are poorly understood and no preventive strategies exist. We sought to determine whether circulating RV-specific CD4+ T-cell responses were modulated in subjects who received probiotic supplementation.

Methods: Our substudy included sixteen HLA-DRB1*0401+ subjects who tested seronegative for RV-39, and who were enrolled in a double-blind placebo-controlled trial of Bifidobacterium lactis Bl-04 supplementation. After 4 weeks of supplementation, subjects received intranasal RV-39. PBMCs isolated on days -28 (pre-supplementation), 0 (pre-inoculation), 5 and 21 (post-inoculation) were stained with HLA-DRB1*0401 tetramers presenting two RV-39 capsid peptides, and analyzed by flow cytometry.

Results: RV-specific CD4+ T-cell frequencies and phenotypes were comparable among probiotic (n=11) and placebo (n=5) groups. Among infected subjects (n=12), RV-specific CD4+ T-cells were expanded during the effector phase (day 5) and displayed an activated effector memory phenotype. This expansion was absent in 2 infected subjects who lacked neutralizing antibodies, and in 4 non-infected subjects. Pre-existing RV-specific memory cells recognized epitopes conserved across RV strains, comprised a mixture of T helper (CXCR5neg) and T follicular helper (CXCR5+) populations, and were predominantly IFN-γ+IL-4neg, with minor IL-17+ and IL-21+ populations. Moreover, they were cross-reactive with a corresponding epitope of RV-16. High pre-existing RV-specific T-cell frequencies were linked to reduced viral infection (p<0.05); however this effect was attenuated after accounting for probiotic supplementation (p=0.11). 

Conclusions: Circulating RV-specific CD4+ T cells display attributes that might be harnessed for the treatment or prevention of common cold.