Streptococcal superantigen-induced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release

Clinical and Experimental Immunology
Frances J. DaviesShiranee Sriskandan

Abstract

Streptococcal pyrogenic exotoxin (Spe) A expression is epidemiologically linked to streptococcal tonsillo-pharyngitis and outbreaks of scarlet fever, although the mechanisms by which superantigens confer advantage to Streptococcus pyogenes are unclear. S. pyogenes is an exclusively human pathogen. As the leucocyte profile of tonsil is unique, the impact of SpeA production on human tonsil cell function was investigated. Human tonsil cells from routine tonsillectomy were co-incubated with purified streptococcal superantigens or culture supernatants from isogenic streptococcal isolates, differing only in superantigen production. Tonsil cell proliferation was quantified by tritiated thymidine incorporation, and cell surface characteristics assessed by flow cytometry. Soluble mediators including immunoglobulin were measured using enzyme-linked immunosorbent assay. Tonsil T cells proliferated in response to SpeA and demonstrated typical release of proinflammatory cytokines. When cultured in the absence of superantigen, tonsil preparations released large quantities of immunoglobulin over 7 days. In contrast, marked B cell apoptosis and abrogation of total immunoglobulin (Ig)A, IgM, and IgG production occurred in the presence of SpeA a...Continue Reading

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Citations

Jun 9, 2020·Journal of Family Medicine and Primary Care·Masoud RadmanPooneh Jalali
Jun 30, 2019·Pathogens·Fiona J RadcliffJohn D Fraser
Feb 23, 2021·ACS Pharmacology & Translational Science·Maura C BelangerRebecca R Pompano
Jun 2, 2021·The Journal of Clinical Investigation·Jian ZhengStanley Perlman
Sep 19, 2020·Nature Communications·Matthew K SigginsShiranee Sriskandan
Dec 31, 2021·PLoS Pathogens·Jacklyn R HurstJohn K McCormick

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Methods Mentioned

BETA
flow cytometry
fluorescence activated cell sorter
FACS
transgenic

Software Mentioned

Graphpad Prism

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