Imperial College London
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ProfessorShiraneeSriskandan

Faculty of Medicine, Department of Infectious Disease

Professor of Infectious Diseases
 
 
 
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Contact

 

s.sriskandan

 
 
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Assistant

 

Ms Teyanna Gaeta +44 (0)20 3313 1943

 
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Location

 

8N21ACWBCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Davies:2019:10.1111/cei.13282,
author = {Davies, F and Olme, C and Lynskey, N and Turner, CE and Sriskandan, S},
doi = {10.1111/cei.13282},
journal = {Clinical and Experimental Immunology},
pages = {83--94},
title = {Streptococcal superantigeninduced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release},
url = {http://dx.doi.org/10.1111/cei.13282},
volume = {197},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Streptococcal pyrogenic exotoxin (Spe) A expression is epidemiologically linked to streptococcal tonsillopharyngitis 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 coincubated 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 enzymelinked 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 and other superantigens. In SpeAstimulated cultures, T follicular helper (Tfh) cells showed a reduction in CXC chemokine receptor (CXCR)5 (CD185) expression, but upregulation of OX40 (CD134) and inducible T cell costimulator (ICOS) (CD278) expression. The phenotypical change in the Tfh population was associated with impaired chemotactic response to CXCL13. SpeA and other superantigens cause dysregulated tonsil immune function, driving T cells from Tfh to a proliferating phenotype, with resultant loss of B cells and immunoglobulin production, providing superantigenproducing bacteria with a probable survival advantage.
AU  - Davies,F
AU  - Olme,C
AU  - Lynskey,N
AU  - Turner,CE
AU  - Sriskandan,S
DO  - 10.1111/cei.13282
EP  - 94
PY  - 2019///
SN  - 1365-2249
SP  - 83
TI  - Streptococcal superantigeninduced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release
T2  - Clinical and Experimental Immunology
UR  - http://dx.doi.org/10.1111/cei.13282
UR  - http://hdl.handle.net/10044/1/68103
VL  - 197
ER  -
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