Characterization of Adaptive-like γδ T Cells in Ugandan Infants during Primary Cytomegalovirus Infection.

Jessica Tuengel,Cetare Mohsenzadeh-Green,Gurpreet Aulakh,Alexandra Maslova,Maria Papadopoulou,Soren Gantt,Laura Cook,Sanya Ranchal,Sara Mostafavi,Bing Cai,Peter Van Den Elzen,Hugo Soudeyns,Sibyl Drissler,David Vermijlen

doi:10.3390/v13101987

Abstract

Gamma-delta (γδ) T cells are unconventional T cells that help control cytomegalovirus (CMV) infection in adults. γδ T cells develop early in gestation, and a fetal public γδ T cell receptor (TCR) clonotype is detected in congenital CMV infections. However, age-dependent γδ T cell responses to primary CMV infection are not well-understood. Flow cytometry and TCR sequencing was used to comprehensively characterize γδ T cell responses to CMV infection in a cohort of 32 infants followed prospectively from birth. Peripheral blood γδ T cell frequencies increased during infancy, and were higher among CMV-infected infants relative to uninfected. Clustering analyses revealed associations between CMV infection and activation marker expression on adaptive-like Vδ1 and Vδ3, but not innate-like Vγ9Vδ2 γδ T cell subsets. Frequencies of NKG2C+CD57+ γδ T cells were temporally associated with the quantity of CMV shed in saliva by infants with primary infection. The public γδ TCR clonotype was only detected in CMV-infected infants <120 days old and at lower frequencies than previously described in fetal infections. Our findings support the notion that CMV infection drives age-dependent expansions of specific γδ T cell populations, and provide insight for novel strategies to prevent CMV transmission and disease.

Highlights

To measure differences in γδ T cell frequencies during primary CMV infection, we examined all subjects from our Ugandan longitudinal birth cohort using conventional examined all subjects from our Ugandan longitudinal birth cohort using+ conventional flow cytometry (Figure 2A)
Expression on γδ T cells were all associated with age; CD56 expression showed a expression on γδ T cells were all associated with age; CD56 expression showed a similar similar trend but was not statistically significant (Figure 2B)
We found that CD8α expression on both the Vδ1 and Vδ3 cells was increased with CMV infection in both infants and adults, and expression of CD8α was decreased on Vδ2 T cells in CMV-infected adults (Figure 5)

Summary

Introduction

Cytomegalovirus (CMV) infects most of the world’s population, beginning in early childhood [1]. Postnatal CMV infection is frequently asymptomatic and rarely causes disease in immunocompetent individuals; population-based studies have indicated an association between CMV infection and all-cause mortality [2]. Congenital CMV infection (cCMV) is a major cause of childhood deafness and other neurodevelopmental disabilities [3]. Immunological changes during early life likely play an important role in the differential pathogenesis of CMV infection acquired in utero versus following birth. Infants and young children have weaker control of CMV replication compared to adults, as evidenced by their higher level and longer duration of viral shedding in saliva and urine [4,5]

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