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Biomedical subjects

N Minato

Publications and source records attributed to N Minato.

At least 145 records · Page 8Linked to original sources
PubMed1984

Natural killer-interferon system in patients with preleukaemic states.

The natural killer (NK)-interferon (IFN) system was investigated in patients with preleukaemic states. Endogenous NK cell activity was markedly reduced in all 12 patients studied. No significant correlation was observed between the activity of NK cells and the percentage of blast cells in the peripheral blood or bone marrow. The frequency of large granular lymphocytes (LGL) in lymphocytes of the peripheral blood was not reduced in most patients. The percentage of target binding cells in patients was essentially the same as that in normal controls, and the activity of NK cells from normal donors was not affected by the coexistence of mononuclear cells obtained from the peripheral blood of patients. Furthermore, the alpha-IFN production in response to HeLa cells persistently infected with measles virus was reduced in all patients studied, except for one case with acquired idiopathic sideroblastic anaemia. The augmented activity of NK cells induced by alpha-IFN was variable, but remained at lower levels than the endogenous activity of NK cells in normal controls. These findings suggest that not only the intrinsic defect and reduced number of NK cells but also the dysfunction of the NK-IFN system may be responsible for the reduced activity of NK cells in patients with preleukaemic states.

Adult↗
PubMed1982

Studies of the function of natural killer-interferon system in patients with Sjögren syndrome.

The natural killer (NK)-interferon (IFN) system is shown to be significantly involved in the resistance of host to viral infections and to tumours in numbers of animal models (1-4). The patients with Sjögren syndrome (SS) as well as those with collagen diseases were systematically investigated for the functions of NK-IFN system, including endogenous and augmented NK activity, IFN production, and responsiveness of NK cells to IFN stimulation, using virus persistently infected cells (heLa-measles cells) as target and stimulator cells. Although endogenous NK activity was not reduced, augmented NK activity by HeLa-measles cells in vitro was significantly depressed in patients with SS compared with that in age-matched normal controls. The patients with SS had also impaired capacity to produce IFN, which is shown to be a major factor regulating NK activity (5,6) in response to HeLa-measles cells in vitro. In three patients with SS who showed severely depressed NK activity, the effect of exogenous IFN was examined, and virtually no augmentation of NK activity was observed in all cases. Under the same condition, the normal controls demonstrated a dramatic increase in NK activity. The reduced IFN production was observed in all examined patients with SS, whereas impaired augmentation of NK activity by the stimulation with HeLa-measles cells as well as IFN seemed to be more striking in patients with the systemic manifestations of the disease, such as hypergammaglobulinemia and lymphoid hyperplasia. The possible involvement of dysfunction of NK-IFN system in the systemic manifestations of SS is discussed.

Adult↗
PubMed1982

Augmentation of delayed-type hypersensitivity to serum proteins by vesicular stomatitis virus infection in mice: virus-suppressor cell interactions.

The effects of infection with vesicular stomatitis virus (VSV) on delayed-type hypersensitivity (DTH) to heterologous serum proteins were investigated in mice. DTH was induced by a subcutaneous injection of antigen in complete Freund's adjuvant. Infection with VSV at the time of immunization did not affect the level of DTH elicited 3 wk later. Marked augmentation of DTH was observed only when previously immunized mice were infected with VSV simultaneously with restimulation by soluble antigen; either soluble antigen or the virus infection alone was ineffective. The augmentation was specific to the antigen used for the restimulation; in the mouse previously immunized with both bovine serum albumin (BSA) and human alpha-globulin (HGG), DTH to BSA but not to HGG was augmented by injecting soluble BSA and VSV, and vice versa. These results strongly suggest that cells involved in the suppression of DTH manifestation became susceptible to the virus after specific antigenic restimulation and were then eliminated.

Animals↗
PubMed1982

In vitro potentiation of human natural killer cell activity by a streptococcal preparation, OK-432: interferon and interleukin-2 participation in the stimulation with OK-432.

Inasmuch as human natural killer (NK) cell activity was markedly augmented by a streptococcal immunopotentiator, OK-432, both in vivo and in vitro, the mechanism in which OK-432 augmented human NK cell activity was analyzed. Culture supernatants of nonadherent lymphocytes stimulated with OK-432 significantly augmented NK cell activity. Significant activity of both interferon (IFN) (both alpha- and gamma-types) and interleukin-2 (IL-2) was detected in the culture supernatants from nonadherent lymphocytes. Concomitant treatment of supernatants with anti-IFN-alpha antiserum and pH-2 glycine-HCI buffer or the absorption of supernatants with an IL-2-dependent cell line completely abrogated the NK-augmenting activity, whereas the treatment with either one of these resulted in only partial elimination of the activity. These results indicate that OK-432 stimulates human nonadherent lymphocytes to produce IFN and IL-2 and that both factors are primarily responsible for the NK augmentation by OK-432.

Biological Products↗
PubMed1981

On the heterogeneity of murine natural killer cells.

The heterogeneity of cells capable exerting spontaneous cytotoxicity in vitro was explored using antisera to several genetically determined surface markers on mouse lymphocytes. Four phenotypes of cells derived either from fresh or cultured murine lymphoid tissue were found to exert natural killer (NK) activity in vitro. One affector cell subset, termed NKI cells, had the serological phenotype of Thy-1-, Lyt-2-, Qa5+, and lysed measles virus persistently infected target cells (HeLa-Ms) but not P815 mastocytoma cells. It corresponds with the NK cells described in most systems in which lymphoma targets are commonly used. A second subset, with the same target cell specificity, termed NKT is a thymus-independent cell with the phenotype Thy-1+, Lyt-2-, Qa-5+, Ly-5+. A third subset of NK cells, termed T killer (TK) cells deriving from cultures of conventional but not nude mouse spleens, mediated spontaneous cytotoxicity of P815 mastocytoma cells, but not of virus-infected targets. It has a phenotype of Thy-1+, Lyt-2+, Qa-5-, Ly-5+, apparently identical with that of conventional, antigen-specific cytotoxic T lymphocytes. The fourth phenotype of NK cells, termed NKM, derived primarily from cultures of bone marrow, is cytotoxic for HeLa-measles but not P815, and expresses only Ly-5+ among the various markers tested. Beige mice possess normal TK and NKM activities, but had normal NKI, NKT as well as NKM activity. All NK cell subsets express the Ly-5 surface marker. The existence of four phenotypically distinct NK effector cells was strengthened by studies on selective regulation of their activity by two different biological factors. Interferon (IFN) augmented NK activity of primarily one of the subsets examined, the NKI cell; the activity of IFN on NKT cells could not be directly tested, but IFN was without positive effect on TK or NKM cells. In contrast, partially purified IFN-free interleuken 2 (IL-2) augmented the activities of both the TK and NKT subsets, but not of NKI or NKM cell. IL-2 was active in augmenting NK activity in spleen cells obtained from both conventional and nu/nu mice, but was without effect on spleens of nu/nu mice depleted of Thy-1+ cells. These and other data suggest that IL-2 acts primarily, if not exclusively, on THy-1+ cells. These results strengthen the view that natural cytotoxicity in vitro can be mediated by several distinct cell populations under different genetic and regulatory control and indicate the importance of defining and delineating the cell lineages of each and the role of the independent subsets in resistance to virus infections and tumors in vivo.

Animals↗
PubMed1981

Influence of anti-mouse interferon serum on the growth and metastasis of tumor cells persistently infected with virus and of human prostatic tumors in athymic nude mice.

Baby hamster kidney or HeLa cells form tumors in 100% of athymic nude mice. When such cells are persistently infected (PI) with RNA viruses, such as mumps or measles virus, the tumor cells either fail to grow or form circumscribed benign nodules. Neither the parental nor the virus PI tumor cells form invasive or metastatic lesions in nude mice. Previous studies have indicated a correlation between the susceptibility of virus-PI tumor cells in vitro and the cytolytic activity of natural killer (NK) cells and their failure to grow in vivo. Because interferon (IF) is the principal regulatory molecule governing the differentiation of NK cells, it was possible to test the relevance of the IF-NK cell system in vivo to restriction of tumor growth by treatment of nude mice with anti-IF globulin. This treatment was shown to reduce both IF production and NK activity in spleen cells. Both parental and virus-PI tumor cells grew and formed larger tumors in nude mice treated with anti-IF globulin than in control nude mice. The viral-PI tumor cells and the uninfected parental cells formed tumors in treated mice that were highly invasive and often metastatic. Some human tumor types have been notoriously difficult to establish as tumor lines in nude mice (e.g., primary human prostatic carcinomas). When transplanted into nude mice treated either with anti-IF globulin or anti-lymphocyte serum, two prostatic carcinomas grew and produced neoplasms with local invasiveness and some metastases. The results are consistent with the view that interferon may be important in restricting the growth, invasiveness, and metastases of tumor cells by acting indirectly through components of the immune system, such as NK cells.

Animals↗
PubMed1980

Mode of regulation of natural killer cell activity by interferon.

Whereas xenogeneic tumors such as baby hamster kidney or HeLa cells grow in nude mice, the same cells persistently infected with a variety of viruses are rejected. Spleen cells from normal nude mice were found to be induced to produce interferon and to exert natural killer (NK) activity on virus persistently infected (PI) tumor cells, and not on uninfected parental cells in vitro. The phenotype of the interferon-producing cells and the NK effector cells was found to be the same namely, Qa 5(+), Ly 5(+), ganglio-N- tetraosylceramide, with 35 percent of the NK cells also expressing Thy 1.2. NK activity against virus PI tumor cell lines could be nonspecifically augmented both in vivo and in vitro by prior contact with virus PI tumor cells. It was unambiguously demonstrated with chemically homogeneous mouse interferon that interferon, and not a contaminant, was responsible for the augmentation of NK activity in vitro. Studies on the mode of interferon action in augmenting NK activity revealed that the target cell for interferon action was serologically distinct from the NK effector cell. Anti-Ly 5 + complement (C)-treated spleen cells were depleted of NK activity and the ability to produce interferon, but, upon incubation with interferon for 1-3 h, regained both NK activity and susceptibility to anti-Ly 5 + C. Treatment with anti-Qa 5 + C eliminated NK activity, which could not be restored by the addition of interferon. We conclude that interferon produced by Ly 5(+) cells in response to virus PI tumor cells acts on Ly 5(-) precursor cells and induces their differentiation into functional Ly 5(+) NK effector cells.

Animals↗
PubMed1980

Augmentation of delayed-type hypersensitivity by vesicular stomatitis virus infection in mice.

Effects of the infection with vesicular stomatitis virus (VSV) on delayed-type hypersensitivity (DTH) to heterologous erythrocytes were investigated in mice. Infection at the time of immunization resulted in production of high levels of DTH that were specific to the antigen used for immunization. The high level of DTH produced in VSV-infected mice could not be attributed to the nonspecific enhancement of the footpad swelling with the infection. Augmentation of DTH was observed in all strains of the mouse (CBA, BALB/c, C3H/He, and C57BL/6) used. The augmenting effect of VSV infection was not as apparent in adult thymectomized mice in which the level of VSV-replicating T cells was reduced. These results strongly suggest that DTH-mediating T cells are resistant to infection by VSV, and also that there are VSV-sensitive cells that may be engaged in the suppression of DTH. It seems improbable, however, that the cells sensitive to VSV infection represent the suppressor cells themselves, since the enhancing effect was not observed in mice in which the suppressor cells were induced by the administration of high doses of the antigen.

Animals↗
PubMed1979

Mechanism of rejection of virus persistently infected tumor cells by athymic nude mice.

Cell lines known to be tumorigenic in the nude mouse were modified by rendering them persistently infected (P.I.) with a variety of RNA viruses, including measles, mumps, vesicular stomatitis virus, and influenza. Although as few as 100 HeLa or BHK cells produced tumors in 100% of nude mice, as many as 2 x 10(7) of the same cells P.I. with viruses failed to produce tumors. An active host response responsible for restricting the growth of the P.I. cells was suggested by the findings of marked mononuclear cell infiltrates at the inoculation sites and the inability of irradiated nude mice to reject them. An analysis of the in vitro cytotoxic activity of spleen cells from normal nude mice indicated that: (a) P.I. cell lines, but not uninfected cell lines, were susceptible to spontaneous cytotoxicity; (b) in vivo inoculation of P.I. lines induced an enhanced cytotoxic activity for P.I. targets in vitro, and this induction was not specific either for inducing virus or cell line; and (c) the effector cell had the characteristics for natural killer (NK) cells. Although the specificity of recognition of the various P.I. cell lines remains unclear, cold competition experiments indicated that blocking the killing of one P.I. cell line, e.g. HeLa-measles, could be achieved only by unlabeled homologous cells, i.e. HeLa-measles, and not by uninfected cells or other P.I. lines. A variant subline of BHK cells P.I. with VSV was selected for its ability to withstand the rejection process in nude mice. These cells formed metastatic and invasive tumors in nude mice. Although they were the most potent inducers in vivo of NK cell activity against various P.I. targets, they were the most resistant of the P.I. lines to NK cell cytotoxicity in vitro. In this system there was a good correlation between tumor rejection in vivo and susceptibility to NK cells in vitro. The present results suggest that NK cells may play a significant role in both rejection of tumor cells, and in resistance to viruses, particularly persistent infections.

Animals↗
PubMed1978

Virus-replicating T cells in the immune response of mice. II. Characterization of T cells capable of replicating vesicular stomatitis virus.

Immunocytological properties of the splenic T cell (Tv) which develop into virus plaque-forming cells in response to the antigenic challenge in vitro were investigated in relation to the properties of helper T cells and suppressor T cells in antibody response. Tv was observed in spleen around 1 wk after the intravenous injection of mice with 10(7) sheep erythrocytes. This contrasted with the finding that both helper T cells and suppressor T cells developed as early as 3 days after the immunization. Tv was proliferative in response to the antigenic stimulation, whereas helper T-cell activity could be expressed without cell division. Development of Tv to virus plaque-forming cells was much more dependent on macrophages than the generation of helper activity. Tv was found in nylon wool adherent fraction, whereas helper T cell was found in both nylon adherent and nonadherent fractions. Tv belongs to the short-lived and nonrecirculating T-cell population (T1), whereas the major part of helper T cells belongs to the long-lived and recirculating T-cell population (T2). These results strongly suggest that vesicular stomatitis virus infect and replicate in the different subset(s) of T cell(s) to which the major part of helper T cells belong.

Animals↗
PubMed1978

Virus-replicating T cells in the immune response of mice. III. Role of vesicular stomatitis virus-replicating T cells in the antibody response.

The functional role of the T cell (Tv) which can replicate vesicular stomatitis virus (VSV) on activation by the antigen was investigated in antibody response in vitro. By the inoculation of VSV into the culture, marked augmentation of antibody response to sheep erythrocytes (SRBC) was observed in the culture of spleen cells taken more than 3 days after the immunization with SRBC, suggesting that the VSV-susceptible suppressor cells were included in these spleen cells and the activity was eliminated by the effect of VSV. Development of two distinct types of suppressor T cells was revealed in the spleen of mice after the priming with SRBC. First, nylon wool nonadherent (NAd) suppressor T cells found in the spleen cells taken 3 days after immunization, and second, nylon wool adherent (Ad) suppressor T cells found in the spleen cells taken approximately 1 wk after immunization. The activity of nylon Ad suppressor T cells was completely abolished by VSV-preinfection, whereas that of nylon NAd suppressor T cells was unaffected. It was also shown that the helper T-cell activity was not influenced by VSV-preinfection. These results provided direct evidence that nylon Ad suppressor T cell but not nylon NAd suppressor T cell nor helper T cell can actually replicate VSV after antigenic stimulation. Thus it was strongly suggested that Tv represents the nylon Ad suppressor T cells.

Animals↗