RESUMO
The human T-cell leukaemia retrovirus 1 (HTLV-1) causes an aggressive leukaemia and also a non-malignant neurological syndrome - tropical spastic paraparesis [TSP]. The two conditions rarely coincide and it is unclear how the virus apparently leads to such distinct pathologies. We investigated whether deranged antigen presentation by potent dendritic cells (DC) could initiate the "spontaneous proliferation", which characterizes peripheral blood T-cells from HLTV-1 infected patients, in vitro. Mononuclear cells were separated from 7 HTLV-1/TSP patients and 3 HTLV-1 carriers and cultured in 20 æl hanging drops in inverted Terasaki plates. Spontaneous proliferation (measured by 3H thymidine uptake) was respectively 2- and 10-fold that of seronegative controls. Stringent depletion of B cells, macrophages and DCs produced highly purified T-cells whose proliferation was reduced to uninfected normal levels. Adding back the DCs restored excess proliferation (>6-fold), partially blocked by anti-DR antibody. Other cells had no effect. In situ hybridization revealed infection of DCs by HTLV-1. These results suggest that DCs are closely related to pathological T-cell behaviour in TSP patients with less aberrant effects in HTLV-1 carriers. We suggest that DCs are central to the pathogenic T-cell response which probably leads to the paraparesis (AU)
