4-1BB ligand-mediated imbalance of helper 17 T cells and regulatory T cells in patients with allergic asthma.

OBJECTIVES: 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)-ß(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-ß(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.