Regulatory T‐cell function of adult T‐cell leukemia/lymphoma cells

Adult T‐cell leukemia/lymphoma (ATLL) patients are highly immunocompromised, but the underlying mechanism responsible for this state remains obscure. Recent studies demonstrated that FOXP3 , which is a master control gene of naturally occurring regulatory T (Treg) cells, is expressed in the tumor cells from a subset of patients with ATLL. Since most ATLL cells express both CD4 and CD25, these tumors might originate from CD4 + CD25 + FOXP3 + Treg cells, based on their phenotypic characteristics. However, whether ATLL cells actually function as Treg cells has not yet been clearly demonstrated. Here, we show that ATLL cells from a subset of patients are not only hypo‐responsive to T‐cell receptor‐mediated activation, but also suppress the proliferation of autologous CD4 + non‐ATLL cells. Furthermore, ATLL cells from this subset of patients secrete only small amounts of IFN‐γ, and suppress IFN‐γ production by autologous CD4 + non‐ATLL cells. These are the first data showing that ATLL cells from a subset of patients function as Treg cells in an autologous setting. The present study provides novel insights into understanding the immunopathogenesis of ATLL, i.e. , how HTLV‐1‐infected cells can survive in the face of host immune responses. It also adds to our understanding of ATLL patients' severely immunocompromised state. © 2007 Wiley‐Liss, Inc.