Staphylococcal superantigens and T cell expansions in Wegener's granulomatosis.
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 (Vbeta) 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 Vbeta chains and four SAg-non-binding Vbeta 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.
Popa
E R
ER
Department of Clinical Immunology, University Hospital, Groningen, The Netherlands. e.popa@med.rug.nl
Stegeman
C A
CA
Bos
N A
NA
Kallenberg
C G M
CG
Tervaert
J W Cohen
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D004269:DNA, Bacterial / Q000302:isolation & purification; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology* / Q000302:isolation & purification; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D004269:DNA, Bacterial; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens