4-1BB ligand-mediated imbalance of helper 17 T cells and regulatory T cells in patients with allergic asthma.
OBJECTIVE
To investigate the presence of 4-1BB ligand (4-1BBL) in the peripheral blood of patients with allergic asthma and evaluate its role in controlling the balance between helper 17 T (T(h)17) and regulatory T (T(reg)) cells.


METHODS
Soluble 4-1BBL (s4-1BBL)  was quantified by enzyme-linked immunosorbent assay in plasma from patients with asthma (n = 45) and from healthy control subjects (n = 35). The proportion of monocytes positive for membrane-bound 4-1BBL (m4-1BBL) was determined by flow cytometry. Peripheral blood mononuclear  cells from patients with asthma were incubated with anti-4-1BB monoclonal antibody in vitro. Concentrations of interleukin (IL)-17 and transforming growth factor (TGF)-β(1) in the culture supernatant were analysed.


RESULTS
Plasma s4-1BBL concentrations and the proportion  of m4-1BBL-positive monocytes were significantly lower in patients with asthma than in control subjects. The culture supernatant concentration of TGF-β(1) was increased and that of IL-17 was decreased by incubation with anti-4-1BB monoclonal antibody.


CONCLUSIONS
Both soluble  and membrane-bound 4-1BBL were reduced in patients with allergic asthma compared with control subjects. 4-1BBL/4-1BB signalling may play an important role in allergic asthma by regulating the T(h)17/T(reg) balance.
Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Ai
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Wan
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Hou
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Zhu
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Tang
D053330:4-1BB Ligand / Q000502:physiology*; D000328:Adult; D001249:Asthma / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D053330:4-1BB Ligand; D020381:Interleukin-17