Journal Article

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

Kwok, William W, Lehtinen, Markus J, Wright, Paul W, Brown, Kenneth B, Woodfolk, Judith A, Turner, Ronald B, Lahtinen, Sampo J, Patrie, James T, Muehling, Lyndsey M

2018

Overview

Circulating virus-specific CCR5+ effector memory CD4+ T cells primed by past exposures to related viruses (1) respond rapidly to rhinovirus and (2) contribute to virus control through enhanced activation and tissue-homing ability. 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.

• Publisher: Oxford University Press
• Subject: Adolescent / Adult / Blood - immunology / Cell Tracking / Enterovirus - immunology / Enterovirus Infections - immunology / Enterovirus Infections - virology / Female / Humans / Immunologic Memory / Major and Brief Reports / Male / Middle Aged / Nasal Mucosa - immunology / Receptors, CCR5 - analysis / Th1 Cells - immunology / Young Adult