Superantigens and Chronic Rhinosinusitis II: Analysis of T-Cell Receptor Vβ Domains in Nasal Polyps

Abstract

Background: The superantigen (SAg) hypothesis of chronic rhinosinusitis (CRS) suggests that toxins within the nose stimulate massive oligoclonal expansion of T-cell populations with subsequent eosinophil recruitment and tissue inflammation. SAgs are capable of activating 1 × 10⁴ more lymphocytes than conventional antigens by binding specific Vβ-domains of the T-cell receptor (TCR). The net effect is skewing from the normal Vβ-profile by oligoclonal expansion of specific domains. This study will assess polyp tissue for evidence of an SAg response in CRS with nasal polyps (CRSwNP). Methods: This study consists of a prospective analysis of 18 CRSwNP subjects undergoing sinus surgery. Flow cytometry was used to analyze the distribution of 24 specific TCR Vβ-domains in lymphocytes from polyp tissue and blood. Evidence of oligoclonal expansion was tabulated for each specimen and defined as mean normative percentage + 2 SD. Results: Eighteen of 18 CRSwNP subjects showed expansion of polyp lymphocytes expressing TCRs with specific Vβ-domains. The average number of Vβ-clones per CRSwNP subject was seven in polyp lymphocytes but only two in blood lymphocytes. Conclusion: The current results indicate that polyp lymphocytes exhibit significant oligoclonal expansion of specific Vβ-domains. These data are considered diagnostic of a SAg effect. The corresponding blood profile is much less, suggesting that the nose is the primary source of stimulus. Although the trigger(s) for this expansion are unknown, these data are consistent with the hypothesis that staphylococcal toxins are central to the development of CRSwNP.