An autoaggressive process against bystander tissues in HTLV-I-infected individuals: a possible pathomechanism of HAM/TSP.
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.
Ijichi
S
S
Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
Izumo
S
S
Eiraku
N
N
Machigashira
K
K
Kubota
R
R
Nagai
M
M
Ikegami
N
N
Kashio
N
N
Umehara
F
F
Maruyama
I
I
D015551:Autoimmunity; D002490:Central Nervous System / Q000276:immunology; D015486:HTLV-I Antigens; D006439:Hemodynamics; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity; D006801:Humans; D007249:Inflammation / Q000209:etiology; D008214:Lymphocytes / Q000502:physiology; D008954:Models, Biological; D015493:Paraparesis, Tropical Spastic / Q000209:etiology* / Q000276:immunology
D015486:HTLV-I Antigens