Single-Cell Tracking Reveals a Role for Pre-Existing CCR5 + Memory Th1 Cells in the Control of Rhinovirus-A39 after Experimental Challenge in Humans

Abstract

Background. Little is known about T cells that respond to human rhinovirus in vivo, due to timing of infection, viral diversity, and complex T-cell specificities. We tracked circulating CD4+ T cells with identical epitope specificities that responded to intranasal challenge with rhinovirus (RV)-A39, and we assessed T-cell signatures in the nose. Methods. Cells were monitored using a mixture of 2 capsid-specific major histocompatibility complex II tetramers over a 7-week period, before and after RV-A39 challenge, in 16 human leukocyte antigen-DR4 + subjects who participated in a trial of Bifidobacterium lactis (Bl-04) supplementation. Results. Pre-existing tetramer + T cells were linked to delayed viral shedding, enriched for activated CCR5 + Th1 effectors, and included a minor interleukin-21 + T follicular helper cell subset. After RV challenge, expansion and activation of virus-specific CCR5 + Th1 effectors was restricted to subjects who had a rise in neutralizing antibodies, and tetramer-negative CCR5 + effector memory types were comodulated. In the nose, CXCR3 + CCR5 + T cells present during acute infection were activated effector memory type, whereas CXCR3 + cells were central memory type, and cognate chemokine ligands were elevated over baseline. Probiotic had no T-cell effects. Conclusions. We conclude that virus-specific CCR5 + effector memory CD4 + T cells primed by previous exposure to related viruses contribute to the control of rhinovirus.