Production of functionally deficient dendritic cells from HTLV-I-infected monocytes: Implications for the dendritic cell defect in adult T cell leukemia

Adult T cell leukemia (ATL) is induced by an infection with human T lymphot ropic virus type I (HTLV-I) and is accompanied by immunodeficiency. Monocyt e-derived immature dendritic cells (DCs) donated by 11 ATL patients were su ppressed in the ability to take up fluorescein isothiocyanate (FITC)-dextra n and were down-regulated in the expression of CD1a and CD86 antigens (Ags) . Monocytes from the patients showed impaired expression of CD14 and HLA-DR Ags. These results suggest intrinsic abnormalities of monocytes and a defe ct of DC maturation in ATL patients. Therefore, we examined the influence o f HTLV-I infection of monocytes on their differentiation to DCs. Monocytes obtained from healthy donors were susceptible to HTLV-I infection in vitro. HTLV-l-infected monocytes were down-regulated in the expression of CD14 Ag s, and immature DCs obtained from them expressed CD1a poorly and were impai red in the ability to take up FITC-dextran. Mature DCs differentiated from these cells could not stimulate autologous CD4(+) T cell or CD8(+) T cell p roliferation, even after being secondarily pulsed with HTLV-I at an immatur e DC stage. These results suggest that HTLV-l-infected monocytes cannot pro perly differentiate to DCs and that this might he one of the important mech anisms producing dysfunctional DCs in ATL patients. (C) 2000 Academic Press .