Unbiased analysis of peripheral blood mononuclear cells reveals CD4 T cell response to RSV matrix protein.

Vaccine: X
Juilee ThakarDavid J Topham

Abstract

Respiratory syncytial virus (RSV) is the most important cause of respiratory tract illness especially in young infants that develop severe disease requiring hospitalization, and accounting for 74,000-126,000 admissions in the United States (Rezaee et al., 2017; Resch, 2017). Observations of neonatal and infant T cells suggest that they may express different immune markers compared to T-cells from older children. Flow cytometry analysis of cellular responses using "conventional" anti-viral markers (IL2, IFN-γ, TNF, IL10 and IL4) upon RSV-peptide stimulation detected an overall low RSV response in peripheral blood. Therefore we sought an unbiased approach to identify RSV-specific immune markers using RNA-sequencing upon stimulation of infant PBMCs with overlapping peptides representing RSV antigens. To understand the cellular response using transcriptional signatures, transcription factors and cell-type specific signatures were used to investigate breadth of response across peptides. Unexpected from the ICS data, M peptide induced a response equivalent to the F-peptide and was characterized by activation of GATA2, 3, STAT3 and IRF1. This along with upregulation of several unconventional T cell signatures was only observed upon M-...Continue Reading

Methods Mentioned

BETA
Enzyme Linked Immunosorbent Assay
flow
ELISA
flow cytometry
RNAseq

Software Mentioned

DAFi
GRSS
Qgen
FlowSOM
limma
IMMPORT Archive
JASPER
QuSAGE

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