Mass Cytometry Defines Virus-Specific CD4 T Cells in Influenza Vaccination.

TitleMass Cytometry Defines Virus-Specific CD4 T Cells in Influenza Vaccination.
Publication TypeJournal Article
Year of Publication2020
AuthorsSubrahmanyam PB, Holmes TH, Lin D, Su LF, Obermoser G, Banchereau J, Pascual V, García-Sastre A, Albrecht RA, Palucka K, Davis MM, Maecker HT
Date Published2020 Dec 11

The antiviral response to influenza virus is complex and multifaceted, involving many immune cell subsets. There is an urgent need to understand the role of CD4 T cells, which orchestrate an effective antiviral response, to improve vaccine design strategies. In this study, we analyzed PBMCs from human participants immunized with influenza vaccine, using high-dimensional single-cell proteomic immune profiling by mass cytometry. Data were analyzed using a novel clustering algorithm, denoised ragged pruning, to define possible influenza virus-specific clusters of CD4 T cells. Denoised ragged pruning identified six clusters of cells. Among these, one cluster (Cluster 3) was found to increase in abundance following stimulation with influenza virus peptide ex vivo. A separate cluster (Cluster 4) was found to expand in abundance between days 0 and 7 postvaccination, indicating that it is vaccine responsive. We examined the expression profiles of all six clusters to characterize their lineage, functionality, and possible role in the response to influenza vaccine. Clusters 3 and 4 consisted of effector memory cells, with high CD154 expression. Cluster 3 expressed cytokines like IL-2, IFN-γ, and TNF-α, whereas Cluster 4 expressed IL-17. Interestingly, some participants had low abundance of Clusters 3 and 4, whereas others had higher abundance of one of these clusters compared with the other. Taken together, we present an approach for identifying novel influenza virus-reactive CD4 T cell subsets, a method that could help advance understanding of the immune response to influenza, predict responsiveness to vaccines, and aid in better vaccine design.

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Alternate JournalImmunohorizons
PubMed ID33310880
PubMed Central IDPMC7891553
Grant ListHHSN272201400008C / AI / NIAID NIH HHS / United States
U19 AI057229 / AI / NIAID NIH HHS / United States
S10 RR027582 / RR / NCRR NIH HHS / United States
U19 AI090019 / AI / NIAID NIH HHS / United States
P01 AI097092 / AI / NIAID NIH HHS / United States

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