Myeloma cells act as tolerogenic antigen‐presenting cells and induce regulatory T cells in vitro

Regulatory T cells ( T regs) are essential for maintenance of self‐tolerance; however, tumor cells can exploit the tolerance to escape the immune system. We investigated the T regs frequency in patients with multiple myeloma ( MM ) and in those with monoclonal gammopathy of undetermined significance ( MGUS ), and found that CD 4 + FoxP3 + and CD 8 + FoxP3 + Tregs were significantly increased in patients with MM and correlated with the active phase. Both Tregs subsets were expanded in cocultures of CD 3 + lymphocytes and fresh CD 138 + MM plasma cells or RPMI 8226 and U266 cell lines and functioned as natural (n) and inducible (i) Tregs insofar as they inhibited the proliferation of stimulated CD 3 lymphocytes via contact‐dependent and contact‐independent pathways. Induction of Tregs by MM plasma cells required a contact‐dependent pathway, implying antigen recognition by T cells. MM plasma cells acted as immature and tolerogenic antigen‐presenting cells ( APC s), in that they displayed low CD 80/ CD 86 expression associated with a phagocytic activity. By acting as immature APC s, MM plasma cells plausibly expand (n)Tregs and (i)Tregs both through conversion of CD 3 + FoxP3 − into CD 3 + FoxP3 + T cells and proliferation of CD 3 + FoxP3 + T cells, which may suppress the anti‐ MM immune response.