An autoaggressive process against bystander tissues in HTLV-I-infected individuals: A possible pathomechanism of [formula omitted

Abstract

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis ( HAM TSP ) is a well-defined clinico-pathological entity in which the virus infection and the host immune responses are involved in the pathomechanism. It is generally agreed that the virus infection precedes the development of HAM TSP and the infection is persistent during the course of disease. However, what plays the key role for the development of HAM TSP remains to be elucidated. In this article, we emphasise the importance of the unique nature of HTLV-I-infected cells, which may have a potential ability to produce viral antigens outside of the blood flow, and we also review a variety of evidences supporting the following proposal. In our hypothesis, the supply of infected T cells from blood flow to central nervous system (CNS) is primary for the development of CNS lesions. Both anatomically determined hemodynamic conditions and adhesion molecule-mediated interactions between circulating infected T cells and endothelial cells may contribute to the localization of the main lesions. Following an induction of the HTLV-I antigens on the surface of infected T cells in CNS compartment, expansion of the responses of immunocompetent T cells against the viral proteins may result in CNS tissue damage which may be mediated by released cytokines. This is the first attempt to implicate a bystander damage mechanism in a human disease as an essential pathomechanism.