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

• Published in: The Journal of infectious diseases Vol. 217; no. 3; pp. 381 - 392
• Main Authors: Muehling, Lyndsey M, Turner, Ronald B, Brown, Kenneth B, Wright, Paul W, Patrie, James T, Lahtinen, Sampo J, Lehtinen, Markus J, Kwok, William W, Woodfolk, Judith A
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 17-01-2018
• Subjects: 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; neutralizing antibodies; CCR5; Th1; rhinovirus; MHCII tetramers
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jix514

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.