S. Ijichi et al., AN AUTOAGGRESSIVE PROCESS AGAINST BYSTANDER TISSUES IN HTLV-1-INFECTED INDIVIDUALS - A POSSIBLE PATHOMECHANISM OF HAM TSP/, Medical hypotheses, 41(6), 1993, pp. 542-547
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
.