Successful development of novel monoclonal antibodies against HTLV-1 bZIP factor and their applications in studying the pathogenesis of HAM/TSP

Background

A recent report has indicated that transgenic expression of HTLV-1 bZIP factor (HBZ) in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice. However, there is limited information on in vivo expression of HBZ in HTLV-1 infected individuals especially HAM/TSP.

Methods

We have generated rat and human monoclonal antibodies against HBZ by hybridoma methodology and a phage display system, and developed the ELISA system for the detection of HBZ protein and anti-HBZ antibodies. Using these reagents, we analyzed the expression of HBZ protein in plasma and peripheral blood mononuclear cells (PBMCs) of HTLV-1 infected individuals as well as HTLV-1 infected cell lines. Then the results were compared with the real time PCR data.

Results

Although we successfully detected HBZ protein in an enforced overexpressed cells and HTLV-1 infected cell lines by flow cytometry, ELISA, immunofluorescence and immunoblotting, we could not detect HBZ protein or anti-HBZ antibodies in HAM/TSP patients and asymptomatic carrires (ACs) by our system. In contrast, HBZ mRNA was significantly elevated in HAM/TSP patients than ACs. Especially, rapidly progressive HAM/TSP patients showed extremely high expression of HBZ mRNA but not tax mRNA in their PBMCs.

Conclusions

These findings suggest that although expression of HBZ protein was suppressed in vivo in HAM/TSP patients and ACs, high expression of HBZ mRNA is closely associated with the pathogenesis of HAM/TSP.