Pathophysiology in CNS

For HAM/TSP disease development, HTLV-I proviral load is an important factor. Recently, a real time quantitative polymerase chain reaction (PCR) assay (TaqMan) was developed 

Histopathological observations have demonstrated that HAM/TSP predominantly affects the thoracic spinal cord 

Collectively, these histopathological studies suggested that an inflammatory process in the central nervous system (CNS) is involved in the pathogenesis of HAM/TSP. 

HTLV-I Tax-specific CDS + CTLs are hypothesized to play an important role in the development of HAM/TSP. Recently, through the development of tetramer technology, HTLV-I Tax-specific HLA-A 0201-restricted CDS + T cells could be readily detected in HLA-A 0201 HAM/TSP patients (Altman et al., 1996 Greten et al., 199S). By using such tetramers, HTLV-I Tax 11-19-specific CDS + cells from the PBMC of HLA-A 0201 HAM/TSP patients were found to represent an 

Several immunologic abnormalities such as increased spontaneous lymphoprohferation, elevated anti-HTLV-I antibody titers in sera and CSF, increased cytokine production, and cellular immune responses have been observed in patients with HAM/TSP. These abnormalities are more often observed in patients with HAM/TSP compared to HTLV-I infected asymptomatic carriers. 

CDS + CTLs in the CNS of HAM/TSP patients was detected by immunohistochemical staining (Anderson et ah, 1990 Umehara et al., 1994b). These stndies support the hypothesis that HTLV-1 infected CD4 + T lymphocytes enter the CNS which may drive local expansion of virus specific CDS + CTLs. These virus-specific T cells may then either directly lyse virus infected cells and/or release a cascade of cytokines and chemokines that resnlt in pathological changes (Fignre 23.5). It is clearly important to define which cells might be targets of CTLs in the CNS. 

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