Immunogenetics and the Pathological Mechanisms of Human T-Cell Leukemia VirusType 1- (HTLV-1-)Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that complex virus-host interactions play an important role in determining the risk of HAM/TSP. This review focuses on the role of the immune response in controlling or limiting viral persistence in HAM/TSP patients, and the reason why some HTLV-1-infected people develop HAM/TSP whereas the majority remains asymptomatic carriers of the virus.

Figure 1

Hypothesis for the pathogenesis of Human T-cell leukemia virus type 1- (HTLV-1-)associated myelopathy/tropical spastic paraparesis (HAM/TSP). In patients with HAM/TSP, genetically determined less efficient CTL response against HTLV-1 may cause higher proviral load and antigen expression, leading in turn to activation and expansion of antigen-specific T cell responses, subsequent induction of large amounts of proinflammatory cytokines and chemokines, and progression of HAM/TSP development. It is also possible that the immunoglobulin G specific to HTLV-1-Tax, which cross-reacts with heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1), is associated with subsequent inflammation following initial tissue damage.