Abstract
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.