Streptococcal superantigen-induced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release.
Adaptive Immunity
Antigens, Bacterial
/ immunology
B-Lymphocytes
/ immunology
Bacterial Proteins
/ immunology
Cell Death
/ immunology
Cell Proliferation
Cytokines
/ metabolism
Exotoxins
/ immunology
Humans
Immunoglobulins
/ biosynthesis
In Vitro Techniques
Lymphocyte Activation
Membrane Proteins
/ immunology
Palatine Tonsil
/ immunology
Phenotype
Streptococcal Infections
/ immunology
Streptococcus pyogenes
/ immunology
Superantigens
/ immunology
T-Lymphocytes, Helper-Inducer
/ immunology
SpeA
antibody
group A streptococcus
streptococcal pyrogenic exotoxin A
streptococcus pyogenes
Journal
Clinical and experimental immunology
ISSN: 1365-2249
Titre abrégé: Clin Exp Immunol
Pays: England
ID NLM: 0057202
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
accepted:
26
02
2019
pubmed:
1
3
2019
medline:
9
4
2020
entrez:
1
3
2019
Statut:
ppublish
Résumé
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 and other superantigens. In SpeA-stimulated cultures, T follicular helper (Tfh) cells showed a reduction in C-X-C chemokine receptor (CXCR)5 (CD185) expression, but up-regulation of OX40 (CD134) and inducible T cell co-stimulator (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 superantigen-producing bacteria with a probable survival advantage.
Identifiants
pubmed: 30815853
doi: 10.1111/cei.13282
pmc: PMC6591145
doi:
Substances chimiques
Antigens, Bacterial
0
Bacterial Proteins
0
Cytokines
0
Exotoxins
0
Immunoglobulins
0
Membrane Proteins
0
SpeA protein, Streptococcus pyogenes
0
Superantigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
83-94Subventions
Organisme : Medical Research Council
ID : G0601399
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© 2019 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.
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