Adult Human T Cell Leukemia

Abstract

Human T cell leukemia virus 1 (HTLV-1), the first characterized human retrovirus, has been identified as the causative agent for adult T-cell leukemia/lymphoma (ATLL). This aggressive lymphoid proliferation is associated with a bad prognosis due to the resistance of HTLV-1-infected cells to most classical chemotherapeutic agents. HTLV-1 is transmitted intravenously, by sexual contact, or through breast-feeding from mother to child, and epidemiological evidence predicts that ATLL development occurs following childhood infection. ATLL exhibits diverse clinical features: the acute, the subacute or smoldering, the chronic forms and the ATL lymphoma. In the two most aggressive forms (acute leukemia and lymphoma), the tumor syndrome comprises massive lymphadenopathy, hepatosplenomegaly, lytic bone lesions and multiple visceral lesions with skin and lung infiltration. HTLV-1 virions infect CD4+ T cells, which represent the main target for HTLV-1 infection in peripheral blood. HTLV-1 associated diseases occur after long periods of virus latency. For years it has been thought that unlike other retroviruses, free virions were poorly infectious. However, a recent study reported that freshly isolated myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) are efficiently and productively infected by cell-free HTLV-1. Furthermore, infected mDC and pDC were able to transfer virions to autologous CD4+ T cells, clearly demonstrating that cell free HTLV-1 can be infectious and target dendritic cells. Innate immune response against HTLV-1 is poorly documented. We describe here immune response against HTLV-1 and physiological consequences.