Dendritic cells from patients with tropical spastic paraparesis are infected with HTLV-1 and stimulate autologous lymphocyte proliferation.
Dendritic cells (DC), important antigen-presenting cells for recruiting T cells into immune responses, are susceptible to infection with HIV-1 and this can cause either stimulatory or suppressive effects on T cells. We examined another human retrovirus, HTLV-1, to determine whether DC were infected and caused any changes in T-cell function. Patients infected with HTLV-1 who have tropical spastic paraparesis (TSP) show high 'spontaneous' lymphocyte proliferation. We studied the basis for this by analyzing the interactions in vitro between lymphocytes and antigen-presenting cells and compared cells taken from HTLV-1-positive TSP patients with those taken from HTLV-1-positive healthy carriers and HTLV-1-negative family members. In HTLV-1-positive individuals, 0.4-5.1% of the DC were infected with HTLV-1 as determined by in situ hybridisation. In TSP patients, depletion of DC and purification of T cells abolished 'spontaneous' lymphocyte proliferation. Reinstating the DC, but not B cells or macrophages, restored proliferation, an effect that was blocked by antibodies either to class II major histocompatibility antigens or to HTLV-1 itself. Thus, presentation of HTLV-1 antigens by infected DC to autologous T cells could result in the abnormal T-cell proliferation and cause the inflammatory reaction leading to tissue damage in TSP. We also speculate that persistent infection of DC with HTLV-1 and consequent continuous stimulation of T cells might be instrumental in the development of HTLV-1-mediated T-cell leukemia.
Macatonia
S E
SE
MRC Clinical Research Centre, Harrow, Middlesex, UK.
Cruickshank
J K
JK
Rudge
P
P
Knight
S C
SC
D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology*; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000382:microbiology