期刊
JOURNAL OF INFECTIOUS DISEASES
卷 217, 期 3, 页码 381-392出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix514
关键词
CCR5; MHCII tetramers; neutralizing antibodies; rhinovirus; Th1
资金
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [T32 AI007496, U01 AI100799, RO1 AI020565]
- Danisco Sweeteners Oy, Kantvik, Finland (part of Dupont Nutrition and Health)
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.
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