We have studied 15 individuals (aged 14-74 years) with antibodies to HTLV-I in their serum and random integration of HTLV-I proviral DNA in their peripheral blood lymphocytes. All but one of these patients suffered from a variety of non-specific complaints which did not correspond to those of adult T-cell leukemia (ATL). All of them were born in Kyushu and Okinawa which are endemic areas for HTLV-I infection; 25% of their family members were also seropositive for HTLV-I. The only haematological abnormality in these patients was the presence of few atypical lymphoid cells in the peripheral blood. The CD4/CD8 ratios were normal but the proportion of Tac positive cells was slightly higher than normal. These individuals with polyclonal integration of HTLV-I proviral DNA seem to represent an intermediate state between smouldering ATL (monoclonal integration) and healthy HTLV-I carriers (with antibodies but no detectable HTLV-I proviral DNA). Patients with this intermediate state of HTLV-I infection may be at risk to progress to ATL. The natural history of HTLV-I infection in humans leading to the development of ATL is reviewed in the light of these new findings.
Patients with hematological malignancies who relapse after bone marrow transplantation (BMT) are often treated with donor lymphocyte infusion. However, this procedure often results in graft-versus-host disease (GVHD). While, Dendritic cells (DCs), which present antigens to naive T cells, have been used in the immunotherapy of cancer, this approach has been logistically difficult due to limiting numbers of DCs. We have now developed a method for obtaining a large number of DCs by treating the granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) from healthy donors with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha). The resulting cells possess the morphologic, phenotypic, and functional characteristics of mature DCs. In in vitro studies, culture of these HLA-matched donor derived-DCs with irradiated each patient's tumor cells as an antigen source, followed by incubation with T cells from the patient, induced the production of highly cytotoxic T lymphocytes (CTLs) specific for the respective tumor cells in the semi-allogeneic setting. A transient, but objective clinical response was obtained in the absence of GVHD when we injected the DCs which had been pulsed with irradiated tumor cells as well as primed T cells from the same original donor of related- allogeneic stem cell transplantation into the relapsed patients. Our findings suggest that treatment of relapsed patients with such donor-derived DCs, and primed T cells may be effective as an adjunctive immunotherapy.
A cytogenetic study was undertaken in 15 cases of Pelger-Huët (P-H) anomaly in 3 families. An enlarged short arm of chromosome 22 (22p+) was found in 14 cases, but in these families 4 cases without P-H anomaly did not show 22p+ in the karyotype. In P-H anomaly, delayed skin hypersensitivity reactions, levels of serum IgG, IgM and IgA, lymphocyte subpopulations, and natural killer and antibody-dependent, cell-mediated cytotoxicity activities were within normal range. The level of serum IgE, mitogen responses in peripheral blood lymphocyte and plaque-forming cell counts were also within normal range with the exception of a case with atopic eczema. Enzymatic activities, nitroblue tetrazolium reduction and phagocytic capacities of neutrophils appeared normal. Abnormalities of neutrophils in cases of P-H anomaly, as compared with normal subjects, were also negative in examinations for chemotaxis and spontaneous migration under agarose and in a membrane filter.
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