Dysfunctional T regulatory cells in multiple myeloma.

Multiple myeloma (MM) is characterized by the production of monoclonal immunoglobulin and is associated with suppressed uninvolved immunoglobulins and dysfunctional T-cell responses. The biologic basis of this dysfunction remains ill defined. Because T regulatory (T(reg)) cells play an important role in suppressing normal immune responses, we evaluated the potential role of T(reg) cells in immune dysfunction in MM. We observed a significant increase in CD4+ CD25+ T cells in patients with monoclonal gammopathy of undetermined significance (MGUS) and in patients with MM compared with healthy donors (25% and 26%, respectively, vs 14%); however, T(reg) cells as measured by FOXP3 expression are significantly decreased in patients with MGUS and MM compared with healthy donors. Moreover, even when they are added in higher proportions, T(reg) cells in patients with MM and MGUS are unable to suppress anti-CD3-mediated T-cell proliferation. This decreased number and function of T(reg) cells in MGUS and in MM may account, at least in part, for the nonspecific increase in CD4+ CD25+ T cells, thereby contributing to dysfunctional T-cell responses.