Pathogenesis

POSSIBLE MECHANISMS FOR THE DEVELOPMENT OF TSP/HAM

INTRODUCTION

In an IgG isolated study, in patients with TSP/HAM, the result was reactive immune for non-infected neurons, and this reactivity was specific for HTLV-I. It suggests that the CNS tissue with monoclonal antibodies for the HTLV- Tax region, an immunodominant antigen from the HTLV-I, reproduce an immunoreactivity for IgG in the TSP/HAM. IgG absorption in TSP/HAM, with HTLV-I Tax recombinant protein or with pre-incubation of the CNS tissue with monoclonal antibodies for the HTLV-I Tax region, abolished the reactivity for IgG in TSP/HAM. These data indicate that patients with TSP/HAM develop a response to antibody in non-infected neuron cells, although the reactivity is blocked by the HTLV-I suggesting viral self-immune reactivity specific to the CNS (18).

HIV-1, a lentivirus that belongs to the same HTLV-I family, has the capacity to produce great amounts of chemokines, such as RANTES (Regulated on Activation, Normal T-cell Expressed and Secreted) MIP-1a, MIP-1ß (inflammatory macrophages which release inhibiting protein), and others, which are natural binding CC-chemokines and CCR-5 receptors (19). These inflammatory proteins demonstrate to have antiviral capabilities are produced by monocytes, T CD8+ cells, and also by Natural Killer cells (NK), during the TSP/HAM evolution (20-22). As a result, it was presumed that an additional mechanism of the TSP/HAM would contribute to the presence of a similar stimulus, such as spinal cord infiltrated cells in some HTLV-I carriers. Furthermore, adhesion molecules such as the lymphocytes associated to antigen-1 (LFA-1), Mac-1, recent antigens (VLA-4), intracellular adhesion molecule 1 (ICAM-1), and vascular cells adhesion molecules 1 (VCAM-1) show a great expression of mononuclear cells in the spinal cord in patients with TSP/HAM. (23).