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Selective Expansion of TCR Vβ2 + Tregs and Impaired Lymphocyte TSST-1 Responsiveness in Bullous Pemphigoid Patients Colonised by Staphylococcus aureus
Journal article   Open access   Peer reviewed

Selective Expansion of TCR Vβ2 + Tregs and Impaired Lymphocyte TSST-1 Responsiveness in Bullous Pemphigoid Patients Colonised by Staphylococcus aureus

Tian Y Chen, Tyler P Crowe, Maryam Fakhimi, Mia Poleksíc, Samuel H Kilgore, Patrick M Schlievert, Janet A Fairley and Kelly N Messingham
Experimental dermatology, Vol.35(9), e70355
09/2026
DOI: 10.1111/exd.70355
PMCID: PMC13591492
PMID: 42765457
url
https://doi.org/10.1111/exd.70355View
Published (Version of record) Open Access

Abstract

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.
 Aged Aged, 80 and over Bacterial Toxins - immunology Case-Control Studies CD4-Positive T-Lymphocytes Cell Proliferation Enterotoxins - immunology Female Forkhead Transcription Factors - metabolism Humans Male Pemphigoid, Bullous - immunology Pemphigoid, Bullous - microbiology Receptors, Antigen, T-Cell, alpha-beta - metabolism Staphylococcus aureus - immunology Superantigens - immunology T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism

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