Staphylococcal superantigens and T cell expansions in Wegener's granulomatosis

• Published in: Clinical and experimental immunology Vol. 132; no. 3; pp. 496 - 504
• Main Authors: POPA, E. R., STEGEMAN, C. A., BOS, N. A., KALLENBERG, C. G. M., TERVAERT, J. W. COHEN
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2003; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Clinical Studies; Cross-Sectional Studies; DNA, Bacterial - isolation & purification; Female; General aspects; Granulomatosis with Polyangiitis - immunology; Humans; Immunopathology; Longitudinal Studies; Lymphocyte Activation - immunology; Male; Medical sciences; Middle Aged; Prospective Studies; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Staphylococcus aureus - immunology; Staphylococcus aureus - isolation & purification; superantigens; Superantigens - immunology; T cells; T-Lymphocyte Subsets - immunology; Wegener's granulomatosis; Human; Cell proliferation; Cardiovascular disease; Wegener granulomatosis; superantigens T cells Wegener's granulomatosis; Cellular immunity; Infection; Vascular disease; Exarcerbation; Vasculitis; Systemic disease; T-Lymphocyte; Bacteriosis; Superantigen; Staphylococcal infection
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2003.02157.x

SUMMARY In Wegener's granulomatosis (WG), a form of autoimmune systemic vasculitis, chronic carriage of Staphylococcus aureus constitutes a risk factor for the development of exacerbations. Circulating T cells in this disease are persistently activated, suggesting the presence of a chronic stimulus. A causal link between chronic carriage of S. aureus and chronic T cell activation in WG is conceivable, because S. aureus produces superantigens (SAg), which are potent T cell stimulators. Superantigenic stimulation of T cells results in expansion of T cell subsets expressing SAg‐binding T cell receptor V‐beta (Vβ) chains. In the present study we hypothesized that in WG the presence of staphylococcal SAg is accompanied by expansion of SAg‐reacting T cell subsets. We tested our hypothesis in a cross‐sectional and a longitudinal study in which the association between seven staphylococcal SAg genes [typed by poplymerase chain reaction (PCR)], eight SAg‐binding Vβ chains and four SAg‐non‐binding Vβ chains (assessed by flow‐cytometry) was assessed. Both studies showed that T cell expansions were present at a significantly higher rate in WG patients than in healthy individuals, but were not associated with the presence of either S. aureus or its SAg. Moreover, T cell expansions were generally of small extent, and did not appear simultaneously in both CD4 and CD8 subsets. We conclude that in WG S. aureus effects its supposed pathogenic function by a mechanism other than superantigenic T cell activation.