Selective Expansion of TCR Vβ2⁺ Tregs and Impaired Lymphocyte TSST-1 Responsiveness in Bullous Pemphigoid Patients...

Bullous pemphigoid (BP) is an autoimmune blistering disease of the elderly who are frequently colonised by Staphylococcus aureus, particularly strains producing the superantigen toxic shock syndrome toxin-1 (TSST-1). Given the ability of TSST-1 to engage the T cell receptor (TCR) Vβ2 chain, we investigated whether superantigen (SAg) exposure in BP is associated with alterations in peripheral T cell populations. CD4⁺ T cells were isolated from peripheral blood mononuclear cells (PBMCs) from BP patients and age-matched healthy controls. T cell responsiveness to TSST-1, staphylococcus enterotoxin G (SEG), and staphylococcus enterotoxin-like-I (SEl-I) was assessed via proliferation assays, and the TCR Vβ repertoire was analysed by RT-qPCR of bulk CD4⁺ T cells and flow cytometry of conventional CD4⁺, CD8⁺, and regulatory T cell (Treg, CD4⁺FoxP3⁺) subsets. Contrary to expectations, proliferative responses to TSST-1 were significantly lower in BP samples than in controls, while responses to SEG and SEl-I were comparable. RT-qPCR revealed no expansion of Vβ2⁺ in bulk CD4⁺ T cells, and surface phenotyping detected no enrichment of Vβ2⁺ cells within conventional CD4⁺ or CD8⁺ T populations. In contrast, Vβ2⁺ cells were selectively enriched within the Treg compartment. These findings indicate that peripheral T cell responses to TSST-1 are attenuated in BP and are associated with subset-specific skewing of the TCR repertoire. These findings are consistent with increased regulatory features in the peripheral immune compartment that may limit systemic SAg reactivity. Studies examining lesional skin immune populations are needed to determine whether local T cell responses differ from those observed in peripheral blood.