Dendritic cells infected in vitro with human T cell leukaemia/lymphoma virus type-1 (HTLV-1); enhanced lymphocytic proliferation and tropical spastic paraparesis

Abstract

SUMMARY Evidence supporting a role of the dendritic cell (DC) in stimulating autologous T cell activity in tropical spastic paraparesis (TSP) was sought by studies of cells taken from healthy volunteers and exposed Vo HTLV-1 in vitro. DC were co-cultured with an HTLV-1 -producing cell line (MT-2) at 1:1 or 10:1 ratios. These DC stimulated high levels of proliferation in autologousT cells. This was similar to that seen in an autologous mixed leucocyte reaction (AMLR) using cells from TSP patients. The requirement for both DC and virus was confirmed. since neither DC co-cultured with uninfected MT-2 cells nor addition of infected MT-2 cells directly to T cells caused significant stimulation. DC exposed to the highest dose of HTLV-1 (1:1) for 24 h before addition of T cells caused strong stimulation that increased after 8 h but almost disappeared by 72 h. In situ hybridization showed that approximately 25% of DC became infected in cultured cells after preincubation for 24 h, and over 50% were infected with a 72-h preincubation. We suggest that infection of DC by HTL V-l may be an initial step in altering the immune system in seronegative patients, and that persistent T cell stimulation in those with genetic susceptibility may underlie the produclion of neurological disease.