Adult T cell leukemia/lymphoma: FoxP3(+) cells and the cell-mediated immune response to HTLV-1

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukaemia/lymphoma (ATLL) in ∼5% of HTLV-1-infected people. ATLL cells frequently express several molecules that are characteristic of regulatory T cells (Tregs), notably CD4, CD25 and the transcription factor FoxP3. It has therefore recently been suggested that HTLV-1 selectively infects and transforms Tregs. We show that HTLV-1 induces and maintains a high frequency of FoxP3+ T cells by inducing expression of the chemokine CCL22; the frequency is especially high in patients with chronic ATLL. In turn, the FoxP3+ T cells exert both potentially beneficial and harmful effects: they suppress the growth of autologous ATLL clones and may also suppress the host's cytotoxic T lymphocyte response, which normally limits HTLV-1 replication and reduces the risk of HTLV-1-associated diseases. Although ATLL cells may exert immune suppressive effects, we conclude that ATLL is not necessarily a tumour of classical FoxP3+ Tregs.