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Biomedical subjects

Y Hinuma

Publications and source records attributed to Y Hinuma.

At least 127 records · Page 7Linked to original sources
PubMed1984

Nature of adult T-cell leukemia-associated membrane antigen on the surface of adult T-cell leukemia virus-carrying cells as revealed by membrane immunofluorescence.

Adult T-cell leukemia-associated membrane antigen (ATLMA) expressed on the surface of living ATL virus (ATLV)-carrying cells was investigated by an indirect membrane immunofluorescence method using natural antibodies to ATLV in human sera. All the ATLV-positive cell lines tested that had cytoplasmic ATL-associated antigen (ATLA) detectable in acetone-fixed cell smears were also positive for ATLMA, but ATLMA was not detected in any ATLV-negative cell lines. The frequencies of ATLA- and ATLMA-bearing cells in seven cell lines tested were roughly parallel. The frequency of expression of both ATLMA and ATLA in cultures of MT-1 cells increased in the presence of 5-iodo-2'-deoxyuridine. All human sera having ATLA antibody had ATLMA antibody and the titers of the two were similar in most of the sera. The anti-ATLMA titers of human sera determined by using an ATLV-bound non-ATL T-cell line as antigen were also similar to the anti-ATLA titers. Absorption of anti-ATLMA-positive sera with living MT-2 cells, in which almost 100% of the cells express ATLA and ATLMA, caused parallel decreases in the anti-ATLA and anti-ATLMA titers. Analysis of the 125I-labeled surface of MT-2 cells by immunoprecipitation with anti-ATLMA-positive human serum followed by gel electrophoresis revealed that p19, p24, p28, and p46 polypeptides were specifically precipitated. These data suggest that ATLMA on the cell surface is not distinguishable from ATLA in the cytoplasm.

Antigens, Surface↗
PubMed1984

Constitutive production of phagocytosis inducing factor(s) in a monocyte/macrophage lineage cell line (THP-1) by retrovirus-transformed human T cell lines.

Four human T cell lines, MT-2, TCL-Kan, TCL-As 2, and TCL-Haz, established from normal leukocytes by cocultivation with adult T-cell leukemia (ATL) virus (ATLV)-producing cells, produced constitutively phagocytosis inducing factor(s) (PIF) that induced phagocytosis in a human monocytic cell line, THP-1. These cell lines expressed ATLV-associated antigens (ATLA) as well as numerous virus particles, whereas the other twelve leukocyte cell lines tested, including T cell lines, B cell lines, and non-T and non-B cell lines, did not produce detectable amounts of the factor(s) in the culture supernatants. PIF was produced in the absence of serum and was not related to either ATLV-particles or viral structural proteins. Its activity was stable at 56 C for 30 min, but labile at 80 C for 30 min and at pH 2 for 20 hr. MT-2 and TCL-Kan produced large amounts of the factor(s) in the culture supernatants but little interferon-gamma (IFN-gamma) or colony stimulating factor (CSF) activity was detected; furthermore, the activity was not neutralized by rabbit anti-IFN-gamma sera. These observations suggest that some ATLV-transformed T cell lines produce PIF that is different from IFN-gamma and CSF.

Cell Line↗
PubMed1984

A new monoclonal antibody recognizing an antigen of human lymphocytes similar or identical to Tac antigen.

A new mouse monoclonal antibody (HIEI, IgG1 type) that reacts with a cell surface glycoprotein of human lymphocytes was isolated. Membrane immunofluorescence assay showed that HIEI, like the anti-Tac monoclonal antibody, reacted preferentially with activated normal human T-cells and adult T-cell leukemia (ATL) virus (ATLV)-carrying human T- and B-cell lines. However, an interesting difference between HIEI and anti-Tac antibody was that HIEI did not react with ATLV-transformed simian cell lines or those cultured with interleukin-2 (IL-2), whereas the anti-Tac antibody did. The immunoprecipitation assay showed that both HIEI and anti-Tac antibody precipitated a glycoprotein with a molecular weight of 60,000 daltons (gp60) from activated normal T-cells and ATLV-positive T- and B-cells, and also gp53 from MT-2 and MT-2-related T-cell lines transformed with ATLV in vitro by the MT-2 cocultivation method. HIEI inhibited the IL-2-dependent proliferation of normal T-cells, but its inhibitory effect was much weaker than that of the anti-Tac antibody. The anti-Tac antibody interfered with the binding of HIEI to target cells, but HIEI did not block binding of the anti-Tac antibody to the cells. These observations indicate that HIEI antibody recognizes a new antigenic determinant of the human Tac antigen.

Animals↗
PubMed1984

Constitutive production and characterization of interferon-gamma in a human T-lymphoblastoid cell line transformed by a human retrovirus.

A human T-lymphoblastoid cell line, TCL-Fuj, constitutively produced a large amount of human gamma interferon (IFN) in culture fluids and has sustained stable IFN production for more than two years. When cells were incubated in RPMI-1640 medium with 10% fetal calf serum for three days, IFN activity was detectable at a cell density of 6 X 10(4) cells/ml, whereas 2,000-16,000 units of IFN per ml were produced at 5-10 X 10(5) cells/ml. IFN production was also detected even in serumfree medium and as early as 2 hr after cultivation in fresh medium. IFN was inhibited by treatment of cells with either actinomycin D or cycloheximide, indicating the requirement of IFN-mRNA and protein for de novo synthesis. The molecular weight of the IFN was 45,000-60,000 as determined by Sephacryl S200 gel filtration. Two activity peaks corresponding to molecular weights of 22,000 and 39,000 were obtained by SDS-polyacrylamide gel electrophoresis. Analysis by isoelectric focusing revealed charge heterogeneity with four species at pIs of 6.0, 7.1, 8.6, and 9.3. Conventional IFN-gamma inducers, concanavalin A and 12-O-tetradecanoyl-phorbol-13-acetate, further enhanced the production of IFN in this cell line.

Cell Line↗
PubMed1984

A retrospective study on transmission of adult T cell leukemia virus by blood transfusion: seroconversion in recipients.

Possible transmission of adult T cell leukemia virus (ATLV) by blood transfusion was studied retrospectively. Of 41 recipients of whole blood or blood components containing cells from donors having antibodies to antigen that is associated with ATLV (anti-ATLA), 26 (63.4%) produced anti-ATLA. However, no anti-ATLA was detected in all 14 recipients of fresh-frozen plasma prepared from anti-ATLA-positive donors. None of 252 recipients of blood with cell components from anti-ATLA-negative donors produced anti-ATLA. The development of anti-ATLA in the recipients may correspond to antibody production after establishment of primary infection with ATLV that is associated with cells in blood from anti-ATLA-positive donors who are ATLV carriers.

Adolescent↗
PubMed1984

A monoclonal antibody that defines p24, a core protein of adult T-cell leukemia virus, and its precursor.

A mouse hybridoma cell line, H15, produced monoclonal antibody reacting with all the adult T-cell leukemia (ATL) virus (ATLV)-bearing cell lines but none of the ATLV-negative cell lines tested. Binding of H15 antibody to ATLV-bearing cell surfaces was specifically blocked by anti-ATLV positive human sera. Radioimmunoprecipitation analyses revealed that the antigen detected by H15 antibody was p24, a core protein of ATLV. Pulse-chase experiments using H15 antibody led to the identification of a protein, p53, which could be a precursor of p24.

Antibodies, Monoclonal↗
PubMed1984

HLA antigens and adult T-cell leukemia virus infection: a community-based study in the Goto Islands, Japan.

In order to study the genetical susceptibility to infection by adult T-cell leukemia virus (ATLV), which is considered to be a main causative agent of adult T-cell leukemia (ATL), the HLA profile of persons with antibody against ATLV-associated antigen (anti-ATLA) was compared with that of antibody-negative persons in villages A and B of the Goto Islands, a typical ATL endemic area in Kyushu, Japan. The frequency (29%) of HLA-B7 in persons with anti-ATLA was significantly higher than that (8%) in anti-ATLA negatives (corrected X2 = 7.73, p less than 0.01) in one village while the frequency of HLA-B7 was around 10% in both positive and negative persons in the other village. These results do not support or deny the possibility of the existence of individuals who are genetically susceptible to ATLV infection in ATL endemic areas of Japan.

Adult↗
PubMed1984

Human retrovirus-induced IL-2 receptors and their possible role in transduction of continuous cell growth signal.

The first half of this report describes direct evidence for the interleukin 2 receptor (IL-2R)-inducing ability of human T-cell leukemia/lymphoma virus (HTLV). When an Epstein-Barr virus (EBV)-transformed human B-cell line, LCL-Kan was infected with HTLV or transfected with plasmid DNA containing defective HTLV genome (long terminal repeat (LTR)-gag-pX-LTR), LCL-Kan cells were altered to express IL-2R which was indistinguishable from that of normal activated T cells. The second half of this paper reports that IL-2 could inhibit proliferation of HTLV-carrying T-cell lines which were spontaneously immortalized from IL-2-dependent cells or peripheral blood cells containing ATL leukemia cells. These results suggest that expression of IL-2R may be induced by HTLV in HTLV-transformed cells, where the IL-2R plays an important role in transduction of continuous cell growth signal.

Cell Division↗
PubMed1984

Specific cytolysis of fresh tumor cells by an autologous killer T cell line derived from an adult T cell leukemia/lymphoma patient.

Cytotoxic T cells (Tc) derived from one patient with adult T cell leukemia/lymphoma (ATL) killed fresh autologous lymphoma cells in vitro. The Tc were induced from peripheral blood leukocytes (PBL) of this patient during remission by multiple in vitro stimulations with an autologous ATLV-bearing cell line (ILT) that was previously established by cloning of PBL in the presence of interleukin 2 (IL 2). PBL from eight other ATL patients were stimulated in the same manner, and responder cells from a patient in remission also showed cytotoxicity specific for ATL virus (ATLV)-bearing cells. Fresh lymphoma cells were obtained in relapse and were used as target cells for the autologous Tc induced. They became susceptible to the Tc within 4 hr of in vitro incubation, and their susceptibility increased with incubation time for at least 12 hr. ATLV antigens on the cell surface of these lymphoma cells, however, were not detected by radioimmunoassay during these incubation periods, but were detectable after 16 hr of incubation. In addition, cytotoxicity against lymphoma cells was completely inhibited by autologous ILT cells used as "cold" target competitor cells. These findings indicate that the target antigen of the Tc was expressed on both autologous ILT cells and lymphoma cells, and it may be different from ATLV antigens detected by serologic methods. In addition, the data suggested allogeneic restriction of the Tc in that the preferentially killed allogeneic ATLV-bearing cells share several HLA antigens.

Adult↗
PubMed1984

Identification of a glycoprotein, gp21, of adult T cell leukemia virus by monoclonal antibody.

A mouse hybridoma cell line producing monoclonal antibody, F10, was established from mice hyperimmunized with cells bearing adult T cell leukemia (ATL) virus (ATLV). F10 antibody reacted with an ATLV structural polypeptide ( gp21 ) with a m.w. of 21,000 that was glycosylated on cell surfaces. The gp21 was expressed on cell surfaces of all ATL-associated antigen (ATLA)-positive human cell lines but not on ATLA-negative cell lines nor peripheral blood leukocytes stimulated with mitogens. The gp21 was also detected with anti-ATLA-positive human serum, and the binding of F10 antibody to ATLA-positive cell surfaces was significantly blocked by pretreatment with anti-ATLA-positive human sera. Double immunofluorescence staining with F10 antibody and anti-ATLA-positive human serum caused co-capping on cell surfaces, which suggests that gp21 co-exists with other ATLV antigens expressed on cell surfaces. Immunoprecipitation studies also suggested that the gp21 is a minor component of the ATLV envelope.

Animals↗
PubMed1983

Adult T-cell leukemia (ATL) virus-specific antibodies in ATL patients and healthy virus carriers.

The adult T-cell leukemia (ATL)-associated antigen complex (ATLA) is recognized by serum antibodies of carriers of ATL virus (ATLV). ATLA consists mainly of ATLV polypeptides and their precursors. The sera from 22 ATL patients, 21 healthy carriers and 9 healthy individuals were examined quantitatively by immunofluorescence assay (IF) for ATLA and by a newly developed radioimmunoprecipitation test with purified 125I-gp68, the putative env gene product of ATLV. More qualitative results were obtained by analysis on polyacrylamide gel (PAGE) of immunoprecipitates from lysates of 35S-cysteine-labelled cells producing ATLV, pelleted ATLV and cell-free culture supernatant. The two quantitative assays gave negative results with sera from all normal subjects and a few patients, but detected ATLA antibodies in all the healthy ATLV carriers. An important finding was that sera of patients that gave negative results in one assay gave positive results in the other, and vice versa. In contrast, all sera from ATL patients and healthy carriers, but not normal donors, precipitated ATLV-specific glycopolypeptides, gp68 and gp46 from 35S-labelled materials. But core polypeptides p28, p24, p19 and p15 were precipitated only by sera with IF titers of over 80. Thus, anti-ATLA antibodies in seropositive sera are predominantly directed against glycopolypeptides of ATLV, and the antibody reactivity to ATLA antigens does not differentiate between ATL patients at various stages of the disease and healthy ATLV carriers.

Antibodies, Neoplasm↗
PubMed1983

Epstein-Barr virus-specific antibodies in patients with adult T-cell leukemia (ATL) and healthy ATL virus-carriers.

Antibodies to Epstein-Barr virus (EBV)-capsid antigen (VCA), early antigen (EA) and EBV-associated nuclear antigen (EBNA) in the sera of 103 patients with adult T-cell leukemia (ATL) and the sera of 243 age- and sex-matched healthy adults, namely 99 anti-ATLA-positive (antibodies to ATL virus-associated antigen) and 144 anti-ATLA-negative individuals, were determined by indirect immunofluorescence. The anti-VCA titers in the sera from ATL patients were within the range observed in healthy controls. Anti-EA was found in 27% of the sera from ATL patients, but in only 8% of the sera from anti-ATLA-negative healthy controls. Antibodies to EBNA, which were present in almost all healthy adults, were not found in 30% of the sera from ATL patients. Of the sera of anti-ATLA-positive healthy adult donors 11% were negative for EBNA antibody. These results suggest that functional impairment of the T-cell system in most ATL patients, and also to a lesser extent in anti-ATLA-positive adults who might be healthy ATLV-carriers, may cause an unusual immune response of antibodies to EBV-associated antigens.

Adult↗