1. Streptococcal superantigen-induced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release.
- Author
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Davies FJ, Olme C, Lynskey NN, Turner CE, and Sriskandan S
- Subjects
- Adaptive Immunity, Antigens, Bacterial immunology, Antigens, Bacterial toxicity, B-Lymphocytes immunology, B-Lymphocytes pathology, Bacterial Proteins toxicity, Cell Death immunology, Cell Proliferation, Cytokines metabolism, Exotoxins toxicity, Humans, Immunoglobulins biosynthesis, In Vitro Techniques, Lymphocyte Activation, Membrane Proteins toxicity, Palatine Tonsil pathology, Phenotype, Streptococcal Infections immunology, Streptococcal Infections pathology, Streptococcus pyogenes pathogenicity, Superantigens immunology, Superantigens toxicity, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Helper-Inducer pathology, Bacterial Proteins immunology, Exotoxins immunology, Membrane Proteins immunology, Palatine Tonsil immunology, Streptococcus pyogenes immunology
- 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 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., (© 2019 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)
- Published
- 2019
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