Human T-lymphotropic virus type 1 (HTLV-1) and innate immunity

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) is a T lymphotropic human retrovirus that causes adult T-cell leukemia/lymphoma (ATL) and is associated with immunological disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A higher viral load in HTLV-1-infected individuals increases the risk of HAM/TSP and ATL; furthermore, it affects the disease severity of HAM/TSP. Therefore, the precise immune mechanisms controlling HTLV-1-infected cells must be further characterized. In this regard, the role of HTLV-1-specific CD8+ cytotoxic T lymphocytes (CTLs) has been studied intensively. However, there are few reports describing the role of innate immunity in controlling the proliferation of HTLV-1-infected cells. Natural killer (NK) and invariant natural killer T (iNKT) cells are the cellular components of innate immunity that regulate the immune response to general viral infection and cancers. Dendritic cells (DCs) play important roles in the activation of these NK and iNKT cells as well as CTLs. In this review, we summarize the characteristics of DCs, NK cells, and iNKT cells in individuals infected with HTLV-1. In the peripheral blood of HAM/TSP and ATL patients, the decreased number and impaired functionality of DCs, NK cells, and iNKT cells have been reported. Even in asymptomatic carriers, the functions of these cell populations are perturbed by HTLV-1 infection, while their frequencies are comparable to those of healthy individuals. These observations suggest that abnormalities of DCs, NK cells, and iNKT cells are implicated in the pathogenesis of HTLV-1-associated diseases via insufficient viral control.