Decreased 4‐1BB expression on CD4+CD25high regulatory T cells in peripheral blood of patients with multiple sclerosis
As a tumour necrosis factor receptor superfamily member, 4‐1BB (CD137) is preferentially expressed in CD4+CD25+ regulatory T cells (Tregs) and has been suggested to play an important role in regulating the generation or function of Tregs. Recent studies of human Tregs have shown that blood CD4+CD25high T cells were much closer to Tregs in terms of their functionality. Furthermore, CD4+CD25high Tregs have been found to have a decreased effector function in patients with multiple sclerosis (MS). In this study, we examined the expression of 4‐1BB and soluble 4‐1BB (s4‐1BB) protein levels in the peripheral blood of MS patients. Compared with healthy controls, MS patients had decreased 4‐1BB expression in their CD4+C25high Tregs and increased plasma s4‐1BB protein levels. Moreover, the plasma s4‐1BB levels of MS patients were shown to be inversely correlated with the 4‐1BB surface expression of CD4+CD25high Tregs. The down‐regulated 4‐1BB expression on CD4+CD25high Tregs of MS patients may be involved in the impaired immunoactivity of these Tregs. The elevated s4‐1BB levels may, at least in part, function as a self‐regulatory attempt to inhibit antigen‐driven proliferation of Tregs or their immunosuppressive activity.