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HTLV-I infection of T and B cells of a patient with adult T-cell leukemia-lymphoma (ATLL) and transmission of HTLV-I from B cells to normal T cells
Authors:Genoveffa Franchini  Dean L Mann  Mikulas Popovic  Randy R Zicht  Robert C Gallo  Flossie Wong-staal
Institution:1. Laboratory of Tumor Cell Biology, Developmental Therapeutics Program National Cancer Institute, Bethesda, MD 20205, U.S.A.;2. Section of Biochemical Epidemiology, Laboratory of Human Carcinogenesis, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20205, U.S.A.
Abstract:We analysed the DNA of different tissues of a patient (HS) with adult T-cell leukemia/lymphoma virus (HTLV-I). We detected viral sequences in fresh specimens from spleen, thymus, liver, skin and peripheral blood neoplastic lymphocytes. The pattern of HTLV-I intergration is identical in the leukemic cells and in all other tissues analysed, but the signal intensity is strongest in the leukemic cells, indicating the source of HTLV-I proviral sequences was the leukemic T-cells which had infiltrated these tissues. In fact, the cultured skin fibroblasts of the patient did not contain HTLV-I sequence. However, cultured lymphocytes of this patient was consistently an immortalized B-cell line containing HTLV-I sequences in a manner indicative of a polyclonal infection. This cell line was also infected with the Epstein-Barr virus (EBV). In order to determine whether HTLV-I alone was sufficient for B-cell immortalization, we obtained single cell clones by limiting dilution. The DNA of all the cell clones that we analysed contained both the HTLV-I and EBV genomes, suggesting that immortalization of the B-cell was more likely due to the EBV rather than HTLV-I. Infectious HTLV-I viruses produced by the B-cell line still had the propensity to infect and transform T-lymphocytes in normal human umbilical cord blood. Unlike the parental B cells, the transformed T lymphocytes were clonally selected. Our results indicate that although the predominant infected cell population of the patient was his leukemic T lymphocytes, some of his EBV-positive B-lymphocytes were also polyclonally infected. The latter had a growth advantage in culture over the T lymphocytes but the virus produced by these immortalized B cells has not been adapted and has maintained its tropism for T cells.
Keywords:HTLV-I  ATLL  HTLV-I and EBV co-infection  HTLV-I transmission  acquired immunodeficiency syndrome  adult T-cell leukemia and lymphoma  Epstein-Barr virus  Human T-cell leukemia lymphoma virus type I  Human T-cell leukemia lymphoma virus type II  Human T-cell leukemia lymphoma virus type III  kilobases  peripheral blood lymphocytes  sodium dodecyl sulphate  sodium saline citrate  T-cell growth factor
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