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Biomedical subjects

M Bennett

Publications and source records attributed to M Bennett.

At least 325 records · Page 18Linked to original sources
PubMed1987

Acute rejection of murine bone marrow allografts by natural killer cells and T cells. Differences in kinetics and target antigens recognized.

Lethally irradiated C.B-17 +/+, C.B-17 scid/scid (severe combined immunodeficiency, SCID), BALB/c-nu/nu (nude), and C57BL/6 (B6) mice were challenged with H-2-homozygous or H-2-heterozygous totally allogeneic bone marrow cell (BMC) grafts. Some of the irradiated mice were immunized simultaneously with large numbers of irradiated marrow and spleen cells syngeneic with the viable BMC transferred. Irradiated SCID and nude mice, devoid of T cells but with normal NK cell function, were able to reject H-2-homozygous BMC grafts within 4 d. However, they were unable to reject H-2-heterozygous BMC allografts by 7 d even if they were immunized. B6 and C.B-17 +/+ mice were able to reject H-2 heterozygous BMC allografts by 7-8 d, but not as early as 4 d, if they were immunized. The rejection of H-2-homozygous BMC on day 4 was inhibited by administration of anti-NK-1.1 antibodies, but not by anti-Lyt-2 antibodies. Conversely, the rejection of H-2-heterozygous allogeneic BMC on day 8 was prevented by anti-Lyt-2 but not by anti-NK-1.1 antibodies. The data indicate that both NK cells and Lyt-2+ T cells can mediate rejection of allogeneic BMC acutely, even after exposure of mice to lethal doses of ionizing irradiation. NK cells appear to recognize Hemopoietic histocompatibility (Hh) antigens on H-2 homozygous stem cells. The inability of SCID and nude mice to reject H-2 heterozygous totally allogeneic BMC indicate that NK cells do not survey donor marrow cells for self H-2 antigens and reject those cells that express nonself H-2 antigens. The T cells presumably recognize conventional H-2 antigens (probably class I) under these conditions.

Animals↗
PubMed1987

Expression of hemopoietic histocompatibility antigens on H-2-loss variants of F1 hybrid lymphoma cells: evidence consistent with trans gene regulation.

H-2 heterozygous marrow stem cells, lymphoid progenitor cells, and leukemia/lymphoma cells do not express hemopoietic or hybrid histocompatibility (Hh) antigens, which are important transplantation antigens recognized during the rejection of normal or neoplastic hemopoietic cells. The Hh-1b determinant of the H-2b haplotype maps to the D region of H-2. We have tested the hypothesis that gene(s) at or near H-2D of the H-2d haplotype down-regulate the expression of Hh-1b in the trans configuration. We used Abelson leukemia virus-transformed pre-B lymphoma cells (ACCb) of BALB/c X BALB.B (H-2d X H-2b) origin, as well as variant lines of ACCb, which were selected for resistance to monoclonal anti-H-2 antibodies plus complement. B6D2F1 (H-2b X H-2d), C3B6F1 (H-2k X H-2b), or B6 (H-2b) mice were infused with inocula of 5 X 10(6) B6 bone marrow cells (BMC). Proliferation of donor-derived marrow cells was judged in terms of DNA synthesis by measuring the splenic incorporation of 5-iodo(125I)-2'-deoxyuridine (IUdR) 5 days after cell transfer. B6 BMC grew much better in B6 than in F1 hybrid host mice, an expression of "hybrid resistance". As observed previously, the injection of EL-4 (H-2b, Hh-1b) tumor cells prior to infusion of B6 (H-2b, Hh-1b) BMC enhanced the growth of B6 BMC in F1 hybrid mice. Therefore, this in vivo "cold target cell competition" type of assay can be used to detect the expression of Hh-1b antigens. Unlike EL-4 (H-2b) cells, hybrid resistance was not affected by prior infusion of (H-2b X H-2d) heterozygous ACCb cells. In contrast, three ACCb variant cell lines, H-2d-, Ld-Dd-, and Dd-, enhanced the growth of B6 BMC in F1 hosts. The ACCb H-2b- cell line did not affect hybrid resistance to B6 BMC. The loss of gene expression on the H-2d chromosome at or very near the H-2Dd locus is correlated with the appearance Hh-1b, as determined by the in vivo cold target competition assay. These results support the hypothesis that heterozygous cells possess trans-acting, dominant, down-regulatory genes mapping near H-2D that control the Hh-1 phenotype of lymphoid tumor cells.

Animals↗
PubMed1987

Rejection of bone marrow allografts by mice with severe combined immune deficiency (SCID). Evidence that natural killer cells can mediate the specificity of marrow graft rejection.

C.B-17 scid (H-2d) mice are homozygous for the gene that causes severe combined immune deficiency (SCID). These mice have no T or B cell function, yet display normal natural killer (NK) activity. Irradiated SCID mice were challenged with marrow grafts to determine if antibodies are necessary for marrow allograft rejection. SCID mice rejected H-2/Hh-1 allogeneic marrow grafts. Moreover, this rejection capability could be adoptively transferred using SCID marrow as a source of NK progenitors infused into irradiated B6 (H-2b) hosts. We conclude that NK cells can mediate marrow allograft reactivity in the absence of immunoglobulin. It follows that NK cells probably have specific receptors for Hh antigens.

Animals↗
PubMed1987

T cell receptor genes do not rearrange or express functional transcripts in natural killer cells of scid mice.

The lineage of natural killer (NK) cells is poorly understood. To examine the relationship between NK cells and cells of the T lineage we have examined purified NK cells from a mutant mouse strain (scid) with severe combined immunodeficiency. Approximately 40% of the lymphoid cells in the spleens of scid mice expressed the NK-specific marker NK-2.1. All NK activity of the scid spleen cells could be accounted for by the NK-2.1+ population, similar to results obtained by using normal C57BL/6 X DBA/2 (B6D2F1) mice. Sorted NK-2.1+ cells proliferated in response to human recombinant interleukin 2 (r-IL 2) but not to concanavalin A (Con A), and were maintained in culture for 2 to 3 wk. Cultured NK-2.1+ cells displayed a cell surface phenotype (Asialo-GM1+, Thy-1.2+, L3T4-, Lyt-2-) and lytic activity similar to that described for freshly isolated NK cells of normal mice. Furthermore, T cell receptor (TCR) genes of the TCR-gamma and TCR-beta loci were in germline configuration, and no functional transcripts of TCR-gamma, TCR-beta, or TCR-alpha were detected. We propose that the expression of the TCR is not necessary for functional NK activity, and NK cells are distinct from both mature cytotoxic T lymphocytes and the earliest identifiable T cells.

Animals↗
PubMed1987

Natural killer cell suppression of Friend virus-induced preleukemic hemopoietic stem cells.

To determine whether hemopoietic cells infected with Friend polycythemia-inducing spleen focus-forming virus (SFFVp) are conserved or suppressed via natural surveillance in leukemia-resistant adult mice, we engrafted C57BL/6 recipients with isologous transgenic (donor origin marker) or natural killer (NK) cell-deficient B6 beige marrow cells exposed to SFFVp in vitro. Both groups of primary recipients were viremic and nonleukemic. Spleen cells from primary SFFVp-infected chimeras were engrafted into irradiated leukemia-susceptible secondary recipients to reveal dormant leukemia and grew as tumors of donor origin in 8 of 38 (21%) and 33 of 47 (70%) instances, respectively. Treatment of marrow donors and recipients with anti-asialo GM1 serum resulted in the depression of NK cell activity and the rapid development of dormant leukemia. We conclude that NK cells are an effective surveillance mechanism able to suppress SFFVp-induced preleukemic stem cells.

Animals↗
PubMed1987

Dietary fatty acid effects on T-cell-mediated immunity in mice infected with mycoplasma pulmonis or given carcinogens by injection.

To test whether or not diets enriched in w-6 polyunsaturated fatty acids are significantly immunosuppressive, B10.D2, DBA/2, and C3B6F1 mice were fed diets enriched for fatty acids: linoleic (POLY), oleic (MONO), palmitic (SAT), or eicosapentanoic (FISH). The B10.D2 and DBA/2 mice were given injected methylcholanthrene several weeks later, and immune studies were performed several months after carcinogen treatment. In conventional quarters, DBA/2 fed the POLY diet survived poorly, and many were infected with Mycoplasma pulmonis, even if given the vehicle, tractinoin, only. B10.D2 mice survived well unless on the POLY diet and given methylcholanthrene. Nevertheless, only mice on the POLY diet were significantly immunosuppressed, and only T-cell-mediated cutaneous sensitivity reactions were affected. Antibody, natural killer cell, and natural cytotoxic cell responses were not influenced by the diets. The C3B6F1 mice were assessed for immune functions prior to carcinogen (ethylnitrosourea) instillation into the trachea, and no immunosuppression was detected. After instillation, mice on the POLY and MONO diets were suppressed for T-cell cutaneous responses. Deliberate infection with Mycoplasma pulmonis resulted in suppressed cutaneous T-cell responses in the POLY group of C3B6F1 mice, and aspirin partially reversed the immunosuppression. Mice on the FISH diet were resistant to immunosuppression. It is tentatively concluded that diets rich in w-6 polyunsaturated diets, while not directly immunosuppressive, do predispose animals to suppression of certain T-cell-mediated immune responses. This immunosuppression can be "triggered" by infection and/or by exposure to carcinogens.

Animals↗
PubMed1986

Murine natural killer cells do not express functional transcripts of the alpha-, beta-, or gamma-chain genes of the T cell receptor.

Murine natural killer (NK) cells were purified by sorting with the NK cell-specific monoclonal antibody anti-NK-1.1. Sorted NK-1.1+ cells contained all splenic NK activity and could be propagated in human recombinant IL 2 for 3 to 4 wk. Short-term cultured NK-1.1+ cells maintained the cell-surface phenotype, morphologic appearance, and lytic activity characteristic of freshly isolated splenic NK cells. RNA extracted from this purified and propagated population of NK cells was probed for T cell receptor gene transcripts by Northern blot analysis. No functional transcripts of the alpha-, beta-, or gamma-chain genes of the T cell receptor were detected. These data dissociate NK cells from mature cytotoxic T cells, as well as the earliest identifiable cells committed to the T lineage.

Animals↗
PubMed1986

Ecology of orthopoxviruses and use of recombinant vaccinia vaccines.

Little is known of the ways in which orthopoxviruses are maintained in nature, and the role of wild-life reservoirs requires further investigation. This lack of information is important in view of proposals to use as vaccines recombinant vaccinia viruses which carry genes for other immunising antigens. The possibility that such strains may become established in nature, as vaccinia may have in Indian buffaloes, and/or undergo genetic hybridisation with existing orthopoxviruses should be considered.

Animals↗
PubMed1986

Learning deficits occur in young mice following transfer of immunity from senescent mice.

The extent to which immune processes contribute to senescence-related neurological/behavioral impairment was examined using an adoptive transfer procedure. C57BL/6 mice aged 22 to 24 months showed impaired ability for acquisition of an active avoidance response when compared with younger mice aged 3 months. An immunofluorescence assay of the sera of these mice indicated that only sera from the senescent mice reacted with brain antigen. When tested three months following irradiation and receipt of bone marrow/spleen cell suspensions from senescent mice, young mice showed senescence-like serum-brain reactivity and declines in their abilities to acquire learning. Young control mice receiving cell suspensions from age-matched donors showed no evidence of serum-brain reactivity or learning deficits, suggesting that impaired learning was related to acquisition of aged immunity and not a nonspecific effect of the transfer procedure. These findings indicate that immune processes may be involved in the etiology of senescence-related neurological/behavioral dysfunctions.

Aging↗
PubMed1986

Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide: differential susceptibility of human lymphocyte functions.

The coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H2O2 on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H2O2. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H2O2 delivery). At low H2O2 flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H2O2 generation increased, suppression became myeloperoxidase-independent and was mediated by H2O2 alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H2O2. The proliferative response to poke-weed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediate degrees of susceptibility. In all assays, lymphocyte viability was greater than 90%. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocyte functions against oxidative injury by myeloperoxidase and H2O2. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H2O2, and shows, in addition, that monocytes can modulate these interactions.

Cell Adhesion↗
PubMed1986

Transmitter secretion varies between visualized release sites at amphibian neuromuscular junctions.

Living amphibian (Bufo marinus) motor-nerve terminals have been stained and electrophysiological techniques have been used to determine the amount of transmitter secreted at selected release sites of the terminals. High secretion occurs at sites laid down near the origin of the terminals; very low or zero secretion occurs at more distal sites. The results indicate that some release sites may fail to secrete transmitter on arrival of a nerve impulse. It is suggested that functionally silent release sites may exist at synapses in the nervous system.

Animals↗
PubMed1986

Origin and differentiation of natural killer cells. II. Functional and morphologic studies of purified NK-1.1+ cells.

Cells bearing the NK-specific marker NK-1.1 were purified from mouse spleens by utilizing a monoclonal anti-NK-1.1 antibody and cell sorting. In normal adult mice, all of the splenic NK activity against YAC-1 cells was found in the NK-1.1+ fraction, whereas NK-1.1- cells were depleted of NK activity. The NK activity of sorted NK-1.1+ cells was enriched 15- to 30-fold over unfractionated spleen cells. Light and electron microscopic studies of purified NK-1.1+ cells showed a homogeneous population of cells, each containing one to four cytoplasmic granules. Mice whose bone marrow has been destroyed by chronic exposure to 17-beta-estradiol have very low NK activity. However, spleen cells of estradiol-treated mice contained a normal frequency of NK-1.1+ cells which bound to YAC-1 cells, but failed to lyse them even after purification and subsequent exposure to interferon-alpha/beta in vitro. It appears, therefore, that in the absence of intact bone marrow, NK-1.1+ cells may be arrested in a nonlytic and interferon-unresponsive state. Spleens of neonatal mice which have low NK activity were analyzed to ascertain whether immature NK-1.1+ cells, similar to those found in estradiol-treated mice, could be demonstrated. Spleens of 8- to 9-day-old mice also contained NK-1.1+ cells which had very low NK activity even after purification. Sorted NK-1.1+ cells were examined for cytotoxicity in mice whose NK activity was suppressed by pretreatment with Corynebacterium parvum (-15 days). In contrast to cells from estradiol-treated and neonatal mice, NK-1.1+ from mice treated with C. parvum had normal functional activity. Similarly, although NK activity of unfractionated bone marrow cells is low, sorted NK-1.1+ cells were greatly enriched for lytic activity. Thus, we conclude that cell sorting with monoclonal anti-NK-1.1 antibody provides a powerful tool for examining the mechanisms underlying various states of low NK activity, and there exist NK-1.1+, nonlytic, interferon-unresponsive cells which apparently require an intact marrow microenvironment for differentiation into mature, lytic NK cells.

Animals↗
PubMed1986

Poxvirus infection in the domestic cat: some clinical and epidemiological observations.

The clinical findings from 30 cases of feline poxvirus infection in the UK are reviewed and some epidemiological observations described and discussed. In most cases the clinical signs consisted of skin lesions only, although systemic signs were also occasionally seen. Over half the cats had a history of a single recent lesion, assumed to be primary, on the head, neck or a forelimb. Twenty-nine of 30 cats developed more widespread secondary skin lesions. Cat-to-cat transmission was apparently rare. More cases were recognised in the autumn than at other times of the year. The possibility of a wild mammal reservoir of infection is discussed.

Animals↗