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Biomedical subjects

S Habu

Publications and source records attributed to S Habu.

At least 145 records · Page 8Linked to original sources
PubMed1983

Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo.

The role of natural killer (NK) cells in the natural resistance of mice to infections by several viruses was examined. Mice were specifically depleted of NK cells by i.v. injection of rabbit antiserum to asialo GM1, a neutral glycosphingolipid present at high concentrations on the surface of NK cells. Control mice were left untreated or were injected with normal rabbit serum. Four to 6 hr later, these mice were infected with lymphocytic choriomeningitis virus (LCMV), mouse hepatitis virus (MHV), murine cytomegalovirus (MCMV), or vaccinia virus. The mice were sacrificed 3 days post-infection and assayed for virus in liver and spleen, spleen NK cell activity, and plasma interferon (IFN). All mice treated with anti-asialo GM1 antibody had drastically reduced NK cell-mediated lysis. Correlating with NK cell depletion, these mice had significantly higher (up to 500-fold) titers of MCMV, MHV, or vaccinia virus in their livers and spleens as compared to control mice. NK cell-depleted MCMV and MHV-infected mice had higher levels of plasma IFN than controls, correlating with the higher virus titers. These NK cell-depleted, virus-infected mice had more extensive hepatitis, assayed by the number of inflammatory foci in their livers, as compared to control virus-infected mice; these foci were also larger and contained more degenerating liver cells than those in control mice. In contrast to the results obtained with MHV, MCMV, and vaccinia virus, NK cell depletion had no effect on virus titers in the early stages of acute LCMV infection or during persistent LCMV infection. Mice depleted of NK cells had similar amounts of LCMV in their spleens and similar plasma IFN levels. Because this antibody to asialo GM1 does not impair other detectable immunologic mechanisms, these data support the hypothesis that NK cells act as a natural resistance mechanism to a number of virus infections, but suggest that their relative importance may vary from virus to virus.

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PubMed1983

Role of natural killer cells against tumor growth in nude mice--a brief review.

To determine the in vivo function of natural killer (NK) cells against tumor development, we used nude mice deprived of NK activity by injection of anti-asialo GM1. We present here the enhancement of transplanted tumor growth in such mice and discuss the role of NK cells in the tumor-host system based on our recent studies.

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PubMed1982

Role of NK cells in the control of metastatic spread and growth of tumor cells in mice.

The ability of BALB/c nude and C57BL/6 mice to eliminate tumor cells from the blood stream was severely impaired after a single inoculation of 0.2 ml of anti-asialo BMI (asGMI) serum, diluted 1:40 to 1:320. The number of i.v.-inoculated YAC-I cells surviving in the lungs of BALB/c nude mice pretreated with anti-asGMI serum was 28 times higher than in the control nude mice. In this respect, nude mice treated with anti-asGMI behaved similarly to beige mice. The increase in the initial survival of tumor cells in the mice that was induced by pre-treatment with anti-asGMI resulted in a substantial increase in the number of artificial lung metastases that developed. In C57BL/6 +/+ mice treated with anti-asGMI and in C57BL/6 beige mice, i.v. inoculation of B16 melanoma cells induced 10 times more metastatic foci in the lungs than in the control C57BL/6 +/+ mice. In contrast, in nude mice which possess higher levels of NK reactivity, metastatic growth was suppressed 7-fold in comparison with intact C57BL/6 +/+ mice. In beige mice and in C57BL/6 +/+ mice treated with anti-asGMI, multiple metastatic foci developed in the liver, whereas in control C57BL/6 +/+ and nude mice, no extrapulmonary metastases were found. These data indicate that B16 melanoma cells are able to grow in the liver, but their growth is ordinarily prevented by NK cells. The antimetastatic defense of C57BL/6 mice treated by anti-asGMI could be restored by transplantation of 40 X 10(6) normal spleen cells. This antimetastatic effect of transplanted spleen cells was mediated by asGMI-bearing cells, since after in vitro pre-treatment of normal spleen cells with anti-asGMI and complement, they lost their ability to inhibit the development of artificial metastases in the lungs of C57BL/6 mice. Suppression of NK reactivity by multiple injections of anti-asGMI (every 4 to 5 days), in C57BL/6 mice inoculated intrafootpad (i.f.p.) with B16 melanoma or 3LL tumor cells, did not influence the growth of local tumors, but dramatically accelerated the development of spontaneous pulmonary metastases. These data demonstrate that NK cells may play an important role in resistance to the dissemination of tumor cells, and therefore contribute to the control of metastasis formation in mice.

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PubMed1982

Morphology and function of ganglio-N-tetraosylceramide-positive lymphocyte mediators of natural killer activity.

More than 90% of nylon wool-passed spleen cells from nude mice reacted with ganglio-N-tetraosylceramide (asialo GM1) which eliminated mouse natural killer (NK) cell activity in the presence of complement. The successful enrichment of asialo GM1-positive (asialo GM1+) cells made possible the demonstration that the number of asialo GM1+ cells was correlated with NK cell activity as well as with binding frequency to YAC-1 target cells. Morphologically, by light and immunoelectron microscopic examinations, the enriched asialo GM1+ cells were composed of 90% lymphocytes and 10% large cells with the characteristics of monocytes. However, the asialo GM1+ lymphocytes (but not the monocytes) bound to the target cells and gave rise to the asialo GM1+ monocytes were sometimes observed to bind to target cells, cytolytic features of the target cells were not demonstrated. These results strongly suggest that asialo GM1+ lymphocytes are essential for NK cytolysis by directly binding to target cells.

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PubMed1982

Distribution of asialo GM1 in lymphoid cells in thymus.

The quantitative change of asialo MG1 on the surface of mouse thymocytes was demonstrated in various ontogenic differentiation stages by immunoelectron microscopic study. Detection of asialo GM1 was performed using anti-asialo GM1 prior fixation in the mixture of glutaraldehyde and paraformaldehyde. Anti-asialo GM1 react with unit membrance of perinuclear space and Golgi complex in the thymocytes which express asialo GM1 on the surface. Those anti-asialo GM1 reaction products observed on the surface and intracellular structures disappeared by ethanol- or methanol-treatment but mostly remained by acetone-treatment. These results suggest that anti-asialo GM1 react to the similar antigen determinants both on the surface and in the cytoplasm which are composed of carbohydrate and lipid.

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PubMed1981

T cells in a suppressor circuit and non-T:non-B cells bear different I-J determinants.

T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determinant (e.g., J1) which is distinct from that (e.g., J2) found on non-T:non-B accessory cells. T-cell subsets examined include Ly-1 inducer and Ly-1,2 acceptor cells which collaborate to generate suppressor activity in the in vitro sheep red blood cell antibody system. Non-T:non-B accessory cells examined include accessory cells involved in concanavalin-A induced, T-cell proliferative responses and in in vitro antibody responses to sheep red blood cells. These results provide evidence for serologic and genetic complexity of the I-J subregion of the murine H-2 gene complex.

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PubMed1981

A non-T:non-B cell bears I-A, I-E, I-J, and Tla (Qa-1?) determinants.

A non-T:non-B accessory cell in peritoneal washout or spleen-cell suspensions facilitates T-cell proliferative responses to the mitogen, concanavalin A. Utilizing monoclonal antibody, we show that this accessory cell bears the same I-A- and I-E-subregion controlled determinants as found on B cells. In addition, the same accessory cell bears a Tla(Qa-1?)-region and an I-J-subregion controlled determinant. This I-J determinant is also present on splenic accessory cells involved in in vitro antibody responses to sheep red blood cells. Data in a companion paper show that not all anti-I-J sera contain antibody reactive with the accessory cell, and suggest that T cells involved in the generation of suppressor activity and accessory cells bear different I-J-subregion controlled determinants.

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PubMed1981

In vivo effects of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice.

Intravenous injection of anti-asialo GM1, which has been shown to eliminate natural killer (NK) activity in vitro in the presence of complement, completely abolished NK activity against lymphoma cell line (YAC-1) in spleen cells from athymic nude mice as well as from conventional mice. An immunofluorescence study revealed a decreased number of asialo GM1 positive cells in the spleens of mice injected with anti-asialo GM1 than in those of mice injected with normal rabbit serum. In the nude mice with reduced NK activity, incidence of tumor take and the growth were enhanced when syngeneic (RL male-1), and allogeneic (YAC-1) tumors and human tumors were transplanted subcutaneously. These results strongly suggest that NK cells play an important role in transplanted-tumor growth in vivo.

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PubMed1980

The glycolipid asialo GM1 as a new differentiation antigen of fetal thymocytes.

Antibody directed to the neutral glycolipid "asialo GM1" was found to react with the majority of thymus lymphoid cells lacking characteristic T cell markers in mice at an early embryonic stage (13 days of gestation). The proportion of these asialo GM1-positive cells (asialo GM1+ cells) decreased strikingly thereafter, contrasting with an increased fraction of lymphocytes possessing T cell surface markers such as Thy-1, Lyt-1, and Lyt-2. After about 18 gestational days, only a few asialo GM1+ cells were detected in the thymus as well as in other lymphoid organs. Double-staining analysis of the embryonic thymocytes (13 days of gestation) with anti-asialo GM1 and anti-Thy-1 demonstrated that thymocytes stained with anti-asialo GM1 did not react with anti-Thy-1, and vice versa. Morphologic examination by immunoelectronmicroscopy demonstrated that these asialo GM1+ cells were mainly composed of immature, large lymphoid cells having large nucleoli and relatively abundant cytoplasm with many polysomes. These results suggest that asialo GM1 is present on very early thymocytes and is lost as the mature murine T cell protein antigens Thy-1, Lyt-1, and Lyt-2 develop on these cells. The antibody to this glycolipid is a useful tool for studying embryonic thymic differentiation.

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PubMed1979

Surface markers on natural killer cells of the mouse.

Rabbit antiserum against mouse brain tissue (anti-brain-associated T cell antigen, anti-BAT) was capable of killing splenic natural killer (NK) cells of CBA/J, BALB/c, C 57 Bl/6J, C 3 H/He and nude mice, which were detected with Molony virus-induced lymphoma (YAC-1) and radiation-induced leukemia (RL male 1) cells as targets. The same antiserum abolished T cell functions, e.g. carrier-specific helper function and the responsiveness to concanavalin A, but not B cell functions, e.g. immunological memory for the secondary antibody response and the responsiveness to lipopolysaccharide. After absorption of the anti-BAT with thymocytes, the ability to kill T cells was completely abrogated, leaving the activity to kill NK cells intact. No other heterologous and isologous antisera, i.e. rabbit anti-mouse thymocyte antiserum, goat antiserum against antigens shared by thymus and B cells, anti-Thy-1.2 and anti-Ia antisera, could eliminate NK function regardless of their definite reactivity against T or B cells. The results indicate that the absorbed anti-BAT can distinguish NK cells from other known subsets of T and B cells.

Animals↗
PubMed1977

Accessory cell dependence of lectin-induced proliferation of mouse T lymphocytes.

Mouse lymph node cells were exposed to carbonyl iron and a magnet to remove phagocytic cells, and passed over Sephadex G-10 and nylon wool and incubated for 12 h on plastic to remove adherent cells and their precursors. More than 99% of the cells in this macrophage-depleted population (which constituted 3-5% of the starting population) were Thy-1+ and Ly-1+, while less than 2% were Ly-2+. These cells usually did not synthesize detectable amounts of DNA when cultured with concanavalin A and responded poorly to phytohemagglutinin. These proliferative responses were completely reconstituted by small numbers of syngeneic or allogeneic peritoneal cells, purified peritoneal macrophages or cells from tertiary cultures of mouse embryo 'fibroblasts', but not by 3T3 cells, P815 mastocytoma cells or Nulli SCC-1 embryonal carcinoma cells, or by 2-mercaptoethanol. The reconstituting peritoneal cells were Thy-1--, Ia+ and present in nu/nu mice; although they had to be alive to reconstitute, they did not have to divide. These results are consistent with the hypothesis that T cell proliferation induced by lectins, like that induced by antigens, may involve the dual recognition of stimulating ligand in association with major histocompatibility complex (Ia) determinants.

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PubMed1977

Studies on the generation of B lymphocytes in fetal liver and bone marrow.

With the use of immunofluorescence techniques, cells containing cytoplasmic IgM (cIgM+), but lacking detectable surface IgM (sIgM+), have been identified in mouse fetal liver and adult bone marrow as a distinct cell population to sIgM+ B lymphocytes. We have shown that there is a considerable difference in the rate of entry of cIgM+ and sIgM+ cells into DNA synthesis in these locations. Moreover, within the cIgM+ population, the largest cells are the main group entering DNA synthesis. Our results are compatible with the notion that a pool of rapidly proliferating, large cIgM+ cells is present in fetal liver and adult bone marrow and that these cells give rise to populations of smaller cIgM+ cells, which move out of cell cycle, and convert to sIgM+ B lymphocytes. However, we recognize that this interpretation is speculative. Finally, we have shown that fetal bone marrow is a site of generation of sIgM+ B lymphocytes, but the question as to whether these cells are derived from Ig- precursors within marrow itself remains open.

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