Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection

Authors

Wenjie Jin
Mike Fang
Ismail Sayin
Carson Smith
Jeffrey L Hunter
Brian Richardson
Jackelyn B Golden
Christopher Haley
Kenneth E Schmader
Michael R Betts
Stephen K Tyring
Cheryl M Cameron
Mark J Cameron
David H Canaday

Publication Date

1-1-2022

Journal

Pathogens and Immunity

Abstract

BACKGROUND: CD4+ T cells are a critical component of effective immune responses to varicella zoster virus (VZV), but their functional properties during the reactivation acute vs latent phase of infection remain poorly defined.

METHODS: Here we assessed the functional and transcriptomic properties of peripheral blood CD4+ T cells in persons with acute herpes zoster (HZ) compared to those with a prior history of HZ infection using multicolor flow cytometry and RNA sequencing.

RESULTS: We found significant differences between the polyfunctionality of VZV-specific total memory, effector memory, and central memory CD4+ T cells in acute vs prior HZ. VZV-specific CD4+ memory T-cell responses in acute HZ reactivation had higher frequencies of IFN-γ and IL-2 producing cells compared to those with prior HZ. In addition, cytotoxic markers were higher in VZV-specific CD4+ T cells than non-VZV-specific cells. Transcriptomic analysis of

CONCLUSIONS: In summary, VZV-specific CD4+ T cells from acute HZ individuals had unique functional and transcriptomic features, and VZV-specific CD4+ T cells as a group had a higher expression of cytotoxic molecules including Perforin, Granzyme-B, and CD107a.

Keywords

VZV, Herpes Zoster, T-cell polyfunction, CD4 T cells, transcriptomic