Adult T cell leukemia (ATL) is induced by an infection with human T lymphotropic virus type I (HTLV-I) and is accompanied by immunodeficiency. Monocyte-derived immature dendritic cells (DCs) donated by 11 ATL patients were suppressed in the ability to take up fluorescein isothiocyanate (FITC)-dextran 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 defect of DC maturation in ATL patients. Therefore, we examined the influence of HTLV-I infection of monocytes on their differentiation to DCs. Monocytes obtained from healthy donors were susceptible to HTLV-I infection in vitro. HTLV-I-infected monocytes were down-regulated in the expression of CD14 Ags, and immature DCs obtained from them expressed CD1a poorly and were impaired 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 proliferation, even after being secondarily pulsed with HTLV-I at an immature DC stage. These results suggest that HTLV-I-infected monocytes cannot properly differentiate to DCs and that this might be one of the important mechanisms producing dysfunctional DCs in ATL patients.

The development of human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is closely associated with the activation of T cells which are HTLV-1 specific but may cross-react with neural antigens (Ags). Immature dendritic cells (DCs), differentiated from normal donor monocytes by using recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin-4, were pulsed with HTLV-1 in vitro. The pulsed DCs contained HTLV-1 proviral DNA and expressed HTLV-1 Gag Ag on their surface 6 days after infection. The DCs matured by lipopolysaccharides stimulated autologous CD4+ T cells and CD8+ T cells in a viral dose-dependent manner. However, the proliferation level of CD4+ T cells was five- to sixfold higher than that of CD8+ T cells. In contrast to virus-infected DCs, DCs pulsed with heat-inactivated virions activated only CD4+ T cells. To clarify the role of DCs in HAM/TSP development, monocytes from patients were cultured for 4 days in the presence of the cytokines. The expression of CD86 Ag on DCs was higher and that of CD1a Ag was more down-regulated than in DCs generated from normal monocytes. DCs from two of five patients expressed HTLV-1 Gag Ag. Furthermore, both CD4+ and CD8+ T cells from the patients were greatly stimulated by contact with autologous DCs pulsed with inactivated viral Ag as well as HTLV-1-infected DCs. These results suggest that DCs are susceptible to HTLV-1 infection and that their cognate interaction with T cells may contribute to the development of HAM/TSP.

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In the present report, we describe a case of adult T cell leukemia/lymphoma (ATLL), a 58-year-old woman, successfully treated with interferon (IFN)-α following autologous peripheral blood stem cell transplantation (auto-PBSCT). The patient remains in remission with full performance status for more than 12 months. Auto-PBSCT reduced the abdominal lymphoma mass and IFN-α eliminated residual tumor cells, possibly through the induction of specific T-cell subsets expressing CD3, CD8 on their surfaces and either IFN-γ or tumor necrosis factor (TNF)-α in cytoplasm. We have treated a total of 4 ATLL patients with auto-PBSCT, including the case presented herein. All other patients treated with auto-PBSCT were not followed by adjuvant chemotherapy or cytokine therapy and relapsed within 3 months after auto-PBSCT. This evidence suggests that the therapeutic success of the present case was attributable to the administration of IFN-α immunotherapy following auto-PBSCT.