Superantigens and chronic rhinosinusitis: Skewing of T-cell receptor V beta-distributions in polyp-derived CD4(+) and CD8(+) T cells

Background: Recent studies have suggested that Staphylococcus aureus. secrete superantigenic toxins that play a role in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP). Twenty S. aureus superantigens (SAg's) have been identified, each of which bind the V beta-region of the T-cell receptor (TCR) outside the peptide-binding site. Approximately 50 distinct V beta-domains exist in the human repertoire, and distinct SAg's will bind only particular domains generating a pattern of V beta-enrichment in lymphocytes dependent on the binding characteristics of a given toxin. The aim of this study was to analyze the pattern of V beta-expression in polyp-derived lymphocytes from CRSwNP patients. Methods: Polyps were harvested from 20 patients with CRSwNP and 3 patients with antrochoanal polyps. Flow cytometry was used to analyze the V beta-repertoire of polyp-derived CD4(+) and CD8(+) lymphocytes. Data were analyzed in light of the known skewing associated with SAg exposure in vivo and in vitro. Skewing was defined as a percentage of V beta-expression > 2 SD of that seen in normal blood. Results: Seven of 20 subjects exhibited skewing in V beta-domains with strong associations with S. aureus SAg's. The three antrochoanal polyps failed to show any significant V beta-skewing. Conclusion: This study establishes evidence of S. aureus; SAg T-cell interactions in polyp lymphocytes of 35% of CRSwNP patients. Although these results are consistent with intranasal exposure of polyp lymphocytes to SAg's, additional study is necessary to establish the role of these toxins in disease pathogenesis.