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Biomedical subjects

Y Hinuma

Publications and source records attributed to Y Hinuma.

At least 163 records · Page 9Linked to original sources
PubMed1982

Expression of target antigen for Epstein-Barr virus-specific cytotoxic T cells on BJAB cells freshly infected with EBV.

The target antigen for Epstein-Barr virus (EBV)-specific cytotoxic T cells (Tc) was expressed on BJAB cells exposed to the B95-8 strain of EBV for at least one hour. Ultraviolet-light (UV)-irradiated noninfectious B95-8 virus also induced the target antigen on BJAB cells. Cold target competition tests suggested that the target antigen expressed on EBV-infected BJAB cells was distinct from the lymphocyte-detected membrane antigen (LYDMA) which was also recognized by the EBV-specific Tc and expressed on autologous EBV-Transformed lymphoblastoid cell line (LCL) cells. Neither of these target antigens for EBV- specific Tc was detected on the surface of EBV-genome positive BJAB cells which had been kept in a long term culture after EBV-infection. Thus, the virion antigen, especially the EBV-membrane antigen (MA), is a possible candidate for the target antigen expressed on EBV-infected BJAB cells. Lysis of EBV-infected BJAB cells was inhibited by target cell treatment with anti-beta 2 microglobulin (anti-beta 2M) antibody and induction of the effector Tc was dependent on the donor individual. These results suggested the possibility that the Tc recognizing EBV-infected BJAB cells are restricted by the major histocompatibility complex (MHC).

Animals↗
PubMed1982

Two distinct human cloned T cell lines that exhibit natural killer-like and anti-human effector activities.

Cloned T cell lines from mixed lymphocyte cultures stimulated with autologous Epstein Barr virus- (EBV) transformed lymphoblastoid cell line (LCL) cells were established using a limiting dilution technique in the presence of T cell growth factor (TCGF). The T cell lines included two distinct clones of cytotoxic T cells (Tc) in addition to EBV-specific Tc. A cytotoxic profile of one cloned line was similar to that of endogenous NK cells in peripheral blood. The other cloned Tc line showed an anti-human cytotoxicity. The susceptible targets for this latter Tc line were various human cells, including autologous LCL and peripheral blood lymphocytes (PBL), stimulated with pokeweed mitogen, along with NK-sensitive and NK-resistant cell lines. Weak cytotoxic activity was detected against various xenogeneic cell lines. Furthermore, autologous and allogeneic cloned T cell lines were resistant to killing by the anti-human effector clone. These t wo distinct cloned Tc lines expressed the Leu-1 and Leu-2a antigens, which are markers of suppressor/cytotoxic T cells.

Animals↗
PubMed1982

Heterogeneity of allogeneic restriction of human cytotoxic T cell clones specific for Epstein Barr virus.

Clones of human cytotoxic T cells (Tc) specific for Epstein Barr virus (EBV) were isolated from peripheral blood lymphocyte (PBL) cultures stimulated repeatedly with autologous EBV-transformed lymphoblastoid cell line (LCL) cells in vitro. The method employed to clone EBV-specific Tc was a limiting dilution technique utilizing T cell growth factor (TCGF). The EBV specificity of Tc clones was determined by showing that they were significantly cytotoxic for autologous LCL cells but not for either autologous PBL or (natural killer-sensitive) K-562 cells. Eight EBV-specific Tc clones derived from a single donor exhibited distinct cytotoxic patterns against allogeneic LCL targets. Two clones were cytotoxic to LCL targets sharing both HLA-A26 and B15 antigens with effectors, and killing by two other clones was strongly restricted to autologous LCL cells. The four remaining clones showed cytotoxicities against various allogeneic LCL targets irrespective of HLA antigen expression. Eight EBV-specific Tc clones derived from a second donor also exhibited a wide spectrum of cytotoxicity to allogeneic LcL targets. We conclude that EBV-specific Tc, induced in vitro, consist of a number of clones with respect to restrictions imposed by the major histocompatibility complex. The determinants regulating these restrictions may include not only private HLA antigenic determinants that are defined by the HLA serotyping, but also undefined HLA antigenic determinants.

Antigens, Heterophile↗
PubMed1982

Infectivity dissociated from transforming activity in a human retrovirus, adult T-cell leukemia virus.

Adult T-cell leukemia virus (ATLV)-associated antigen was induced in normal human peripheral or cord lymphocytes by inoculation of cell-free ATLV from a producer line, MT-2. Induction of the antigen was much more efficient, when the cells were treated with phytohemagglutinin before infection. Most ATLV-specific antigen (ATLA)-positive cells induced by ATLV in peripheral lymphocytes formed rosettes with sheep erythrocytes, but 20 to 40% of those induced in cord lymphocytes were not rosette-forming cells. Continuous proliferation of ATLA-positive cells was not observed.

Adult↗
PubMed1982

Epidemiological analysis of the distribution of antibody to adult T-cell leukemia-virus-associated antigen: possible horizontal transmission of adult T-cell leukemia virus.

About 20% of healthy inhabitants in the endemic area of adult T-cell leukemia/lymphoma (ATL) in Nagasaki Prefecture showed a positive antibody to adult T-cell leukemia virus (ATLV)-associated antigen (ATLA), while none of the inhabitants in a non-endemic area in Aichi Prefecture showed a positive anti-ATLA. The age-specific positive rate of anti-ATLA in the endemic area increased with age, especially in females. The positive rate of anti-ATLA among inhabitants older than 40 years was 21% in males and 36% in females. From epidemiological analyses of the mode of anti-ATLA reactivity among married couples and some family members and relatives with positive and negative anti-ATLA, two routes of transmission of ATLV were suggested. One route is from parents to children, either vertically or horizontally, and the other route is horizontal transmission between spouses, especially from husband to wife. The presence of some vectors of ATLV in the endemic area of ATL is discussed.

Adult↗
PubMed1982

A retrovirus from human leukemia cell lines: its isolation, characterization, and implication in human adult T-cell leukemia (ATL).

We have tried to isolate a retrovirus from adult T-cell leukemia (ATL) which is a new clinical entity of T-cell malignancy. This disease shows a peculiar geographic clustering of patient birthplaces in the southwestern part of Japan. A retrovirus was isolated from the T-cell line, MT-2, which was established from cord lymphocytes cocultivated with leukemic cells from an ATL patient and characterized by: (a) density of 1.152-1.155 g/ml in sucrose gradient; (b) reverse transcriptase activity; (c) specific protein components; (d) RNA labeled with 3H-uridine, and (e) specific DNA complementary with viral RNA. The retrovirus was named adult T-cell leukemia virus (ATLV). Complementary DNA (cDNA) prepared by the endogenous reaction of detergent-treated virions hybridized with 35S RNA in MT-2 cells and another ATL cell line, MT-1, and this 35S RNA was inducible with IUDR treatment of the MT-1 cells, indicating that ATLV is a typical retrovirus containing 35S RNA as the genome. However, the cDNA did not show any detectable hybridization with cellular RNA of other human cell lines unrelated to ATL. The ATLV proviral DNA was detected in the chromosomal DNA of MT-1 and MT-2 cell lines as well well as in fresh peripheral blood cells of all five patients with ATL tested; however, it was not found in those of three healthy adults. Furthermore, sera from the patients reacted with one component of the ATLV protein, but normal sera did not. These sera and all other sera from ATL patients were previously shown to react with antigen(s) in leukemic cells of ATL, and the antigen(s) also reacted with sera from about 25% of the healthy adults in the endemic area, but not in the non-endemic area. These close associations of ATLV proviral DNA and proteins with ATL are direct evidence strongly suggesting the involvement of the retrovirus, ATLV, in the leukemogenesis of human ATL.

Adult↗
PubMed1982

[Adult T cell leukemia virus (ATLV)--a serological study].

A nation-wide sero-epidemiologic survey of adult T-cell leukemia virus (ATLV) detected as anti-ATLA (ATLV-associated antigen) was made in Japan. Sera from adult donors in 15 different locations were screened for anti-ATLA. High incidences (6 to 37%) of antibody-positive donors were found in seven regions, one in northern Japan, and the others in southwestern regions. These areas are ATLV-endemic areas corresponding to ATL-endemic areas. Examination of sera from healthy donors aged 6 to 80 years in ATL-endemic areas showed an age-dependent increase of seropositive donors with a maximum of about 30% at 40 years of age. Anti-ATLA was found in all but two of 142 patients with ATL. Anti-ATLA-positive patients with ATL were mainly found in ATLV-endemic areas, and only a few in ATL-nonendemic areas. Six patients with cutaneous T-cell lymphoma in ATLV-nonendemic areas gave a negative reaction for anti-ATLA. The geometric mean titer of anti-ATLA of patients with ATL was higher than that of healthy donors.

Adult↗
PubMed1981

Induction of Epstein-Barr virus by an new tumor promoter, teleocidin, compared to induction by TPA.

The effect of teleocidin, a new, naturally occurring tumor promoter on induction of Epstein-Barr virus (EBV), was compared with that of a known tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Early antigen (EA) and/or capsid antigen (VCA) of EBV was induced in the EBV genome-carrying cell lines C-6 and P3HR-I cells by teleocidin, its effect being maximal at a concentration of 12.5 ng/ml. The production of infectious EBV from P3-HR-I cells was enhanced by teleocidin maximally at a concentration of 0.5 to 2.5 ng/ml. The outgrowth of EBV-transformed cells from peripheral lymphocytes of seropositive healthy donors was also enhanced by teleocidin at a concentration of 0.02 to 0.5 ng/ml. TPA tested simultaneously in all experiments exhibited the same activities as teleocidin, and was effective at similar concentrations. Teleocidin enhanced both EA and VCA synthesis in P3HR-I cells additively with n-butyrate, but not with TPA. This suggests that teleocidin and TPA have a common mechanism of action, although their chemical structures are different.

Alkaloids↗
PubMed1981

Establishment of human cytotoxic T-cell lines specific for Epstein-Barr virus-transformed autologous cells.

EBV-specific cytotoxic T cells (Tc) induced in vitro have continuously proliferated in vitro for over 9 months. The long-term maintenance of the Tc growth was dependent on periodic supplementation of both irrediated EBV-transformed autologous lymphoblastoid cell line (LCL) cels and conditioned medium. The latter was derived from supernatants of human spleen-cell cultures stimulated with phytohemagglutinin. The cultured Tc maintained significant cytotoxic activity to autologous LCL cells but not to EBV-unrelated target cells, including K-562, B-, T-, null-cell lines and mitogen-stimulated antologous peripheral blood lymphocytes. Thus, established EBV-specific Tc lines from five different individuals always exhibited highly significant cytotoxicity against exhibited highly significant cytotoxicity against autologous LCL cells but not always against allogeneic LCL cells. Furthermore, restriction of the Tc to the autologous LCL was more pronounced after long-term culture than it was initially. This suggests that certain clones of Tc which arignificant cytotoxicity against exhibited highly significant cytotoxicity against autologous LCL cells but not always against allogeneic LCL cells. Furthermore, restriction of the Tc to the autologous LCL was more pronounced after long-term culture than it was initially. This suggests that certain clones of Tc which arignificant cytotoxicity against exhibited highly significant cytotoxicity against autologous LCL cells but not always against allogeneic LCL cells. Furthermore, restriction of the Tc to the autologous LCL was more pronounced after long-term culture than it was initially. This suggests that certain clones of Tc which are probably restricted to HLA are selectively established during long-term cultivation.

Antigens, Viral↗
PubMed1981

Mechanisms of enhancement of Epstein-Barr virus-induced transformation of peripheral blood lymphocytes by a tumor promoter, TPA, with special reference to lowering of cytotoxicity of T cells.

The mechanism of the previously observed enhancement of Epstein-Barr virus (EBV)-induced cell transformation of human lymphocytes by 12-0-tetradecanoyl-phorbol-13-acetate (TPA) was studied. A concentration of TPA (0.5 ng/ml) was used. In cultures of human cord blood lymphocytes infected with EBV in the presence of TPA, a larger number of EBV-associated nuclear antigen (EBNA)-positive and/or DNA synthesizing cells was observed than in the absence of TPA. In the virus-infected lymphocyte cultures of EBV-seropositive adult donors, in vitro regression of transformation, which is known to be caused by T lymphocytes, was suppressed by TPA, EBV-specific and -non-specific cytotoxicity of T cells generated in mixed cultures of peripheral blood lymphocytes (PBL) of seropositive adults and autologous lymphoblastoid cell line (LCL) cells was markedly lowered by the presence of TPA in the cultures, However, TPA had little effect on proliferation of T cells in stimulated cultures, and addition of TPA to the reaction mixture for the cytotoxicity test did not lower the cytotoxicity. These results suggest that TPA has an inhibitory effect on T cells which suppress EBV-transformation. THe effect on T cells, together with the direct promoting effect on proliferation of EBV-transformed cells, may explain the outcome of enhancement of EBV-induced LCL establishment from PBL of seropositive donors by TPA previously observed.

Adult↗
PubMed1981

Enhancement of outgrowth of EB virus-transformed cells from normal human peripheral blood by a tumor promoter, TPA.

Effect of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the establishment of lymphoblastoid cell lines (LCL) following spontaneous tranformation of B cells by Epstein-Barr virus (EBV) from peripheral lymphocytes of healthy EBV-seropositive adults was examined. In the lymphocyte culture with TPA (0.5 ng/ml), the frequency of establishment of LCL increased and the time required for appearance of transformation decreased. A larger number of EBV-positive cells in the peripheral blood were detected in the assay by co-cultures with cord blood lymphocytes in the presence of TPA than in the absence of it. The enhancement of LCL establishment by TPA was largely abolished in the culture with EBV neutralizing antibody-containing human umbilical cord serum. This suggests that the enhancement by TPA may be caused mostly by transformation of coresident B lymphocytes infected with active virus induced from the EBV genome-positive cells by TPA.

Adult↗