Follicular helper-like ?d T cells promote plasma cell differentiation in Behçet's disease
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Authors
Mohammed, Sahar Shaaban
Alkhalifah, Abdullah Khalifah S.
Mirza, Rahilah
Okinedo, Sarah-Pristine Omoefe
Inampudi, Rani Aishwarya
Bibi, Azimoon
Senusi, Amal
Pardieu, Claire
McCarthy, Neil E.
Fortune, Farida
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2026
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OBJECTIVES: Behçet's disease (BD) is a systemic vasculitis characterized by recurrent oral and genital ulcers. The disease can manifest diverse phenotypes -such as mucocutaneous, ocular BD- with an uncertain role for autoantibodies in disease pathogenesis. Altered ?dT-cell and B-cell phenotypes have been widely reported in BD, but it remains unknown whether these lineages can interact to promote autoantibody production. METHODS: This study included 75 patients with a BD diagnosis, alongside 41 healthy control (HC) volunteers. We performed ex vivo flow-cytometric profiling of blood ?dT and B cells, established a cell culture system to investigate plasma cell generation in vitro, and quantified anti-HSP60 autoantibody levels in BD and HC participants' serum and cell culture supernatants. RESULTS: BD patients with active disease displayed a significant increase in the frequency of cells CXCR5(+)PD-1(+) Vd2 T cells resembling a follicular helper-like functional state. Upon stimulation, Vd2 T cells from BD patients showed increased expression of ICOS and CXCR5, induced significant B cell proliferation, and promoted differentiation of plasma cells in vitro. Cultures of cells from BD patients contained increased levels of multiple cytokines that can support plasma cell differentiation (IL-4, IL-10, IL-17, CXCL13, TNF-a, IFN-?). Anti-HSP60 autoantibodies were significantly enriched in blood serum from BD patients with active disease as well as the supernatants of patient-derived cell cultures compared to the healthy volunteer cell cultures. CONCLUSION: Our findings suggest that ?dT cells may enhance B-cell differentiation into antibody-producing plasma cells in BD patients with mucocutaneous and ocular clinical phenotypes.
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Frontiers in immunology
Volume
17