AN AUTOAGGRESSIVE PROCESS AGAINST BYSTANDER TISSUES IN HTLV-1-INFECTED INDIVIDUALS - A POSSIBLE PATHOMECHANISM OF HAM TSP/

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropi cal spastic paraparesis (HAM/TSP) is a well-defined clinico-pathologic al entity in which the virus infection and the host immune responses a re involved in the pathomechanism. It is generally agreed that the vir us infection precedes the development of HAM/TSP and the infection is persistent during the course of disease. However, what plays the key r ole for the development of HAM/TSP remains to be elucidated. In this a rticle, we emphasise the importance of the unique nature of HTLV-I-inf ected cells, which may have a potential ability to produce viral antig ens outside of the blood flow, and we also review a variety of evidenc es supporting the following proposal. In our hypothesis, the supply of infected T cells from blood flow to central nervous system (CNS) is p rimary for the development of CNS lesions. Both anatomically determine d hemodynamic conditions and adhesion molecule-mediated interactions b etween circulating infected T cells and endothelial cells may contribu te to the localization of the main lesions. Following an induction of the HTLV-I antigens on the surface of infected T cells in CNS compartm ent, 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 bystan der damage mechanism in a human disease as an essential pathomechanism .