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S Specter

Publications and source records attributed to S Specter.

At least 73 records · Page 4Linked to original sources
PubMed1989

Interleukins 1 and 2 production and responsiveness in the early stages of retroviral infections of mice.

Infection of BALB/c mice with the Friend leukemia complex (FLC) or its helper F-MuLV produced no major changes of IL 1 production and responsiveness but caused profound derangements of IL 2 homeostasis. IL 2 production by spleen cells was severely decreased from the early stages postinfection (pi). By Day 8 the effects of the two viral preparations were similar. Reminiscent of the kinetics of immunosuppression produced by the two viruses, subsequently the effects diverged: in the case of FLC, IL 2 accumulation became progressively lower, while F-MuLV-infected spleen cells produced approximately half the normal levels of IL 2 irrespective of time pi. At Day 8 pi unstimulated spleen cells absorbed enhanced amounts of IL 2, but failed to proliferate in response to it. Unfractionated and adherent spleen cells from infected mice (but not cell-free virus or culture fluids) inhibited the proliferative response of CTLL-2 cells to IL 2, suggesting a "suppressor" function for infected macrophages. Exogenous IL 2 failed to bring in vitro antigen or mitogen responsiveness of infected spleen cells to the levels seen with control cells and did not affect FLC-induced leukemogenesis in vivo.

Animals↗
PubMed1989

Friend leukemia complex infection of mice as an experimental model for AIDS studies.

It is now clear that AIDS results from a complex pathogenesis where virus-induced cytopathology represents only one of the contributing factors, while the others remain elusive. For this and other reasons there is much interest in the mechanisms whereby other classically immunodepressive noncytocidal retroviruses, such as viruses of the murine Friend leukemia complex (FLC), affect the immune system. FLC-induced immunosuppression has already provided important leads to the understanding of the mechanisms whereby retroviruses immunosuppress their hosts. It is expected that further investigation of the model will prove useful in several areas of AIDS research, including the development of efficacious drug therapies.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Prevention and reversal of delta-9-tetrahydrocannabinol induced depression of natural killer cell activity by interleukin-2.

The effects of delta-9-tetrahydrocannabinol (THC) on NK cell activity were studied. Previously, we reported that incubation of human peripheral blood mononuclear cells in THC resulted in an inhibition of natural killer (NK) cell activity. The present study examined the mechanism(s) of the decrease in NK cell activity. The inhibition of killing by NK cells was not due to a failure of NK cells to bind to K562 target cells. Furthermore, indomethacin did not abrogate the THC-mediated effect, suggesting that prostaglandins are not involved in the process leading to suppression of NK cell activity. However, NK activity was partially restored if cells, pretreated with THC, were washed to remove excess drug and then incubated overnight in fresh medium before assay. Addition of 1-100 U IL-2, either during pretreatment with THC or during overnight incubation, precluded or promoted the reversal of the inhibition of NK cell cytotoxicity. We conclude that the regulatory mechanism(s) involved in depression of NK cell cytotoxicity by THC is significantly influenced by IL-2.

Adolescent↗
PubMed1988

Non-toxic endotoxin polysaccharide induces soluble mediators which potentiate antibody production by murine retrovirus-suppressed splenocytes.

Mice infected with Friend leukemia virus show marked acquired immunodeficiency characterized by the impairment of immune function of spleen cells to various antigens, both in vivo and in vitro. The large mol. wt. endotoxin derived from Serratia marcescens, as well as a smaller non-toxic polysaccharide derivative, were found to augment the antibody responsiveness of spleen cells from normal as well as FLV-infected mice. In addition, serum from normal donor mice pretreated with BCG and injected either with endotoxin or the polysaccharide derivative potentiated the antibody response of spleen cells from both normal and FLV-infected mice. Similar enhancement was induced by "antibody response helper factor(s)" present in 3-5 day spleen culture supernatants from endotoxin or polysaccharide-treated spleen cells from normal mice. Enhancement of the antibody response of spleen cells from FLV-infected mice by the antibody helper activity was due to stimulation of B-lymphocytes and reversal of a defect in antibody helper factor(s) formation by macrophages. Similar antibody response enhancing activity was induced by both endotoxin and the non-toxic polysaccharide derivative in cultures of normal spleen cells, adherent spleen cell populations, peritoneal cells and the P388D1 macrophage cell line.

Animals↗
PubMed1988

Suppression by delta-9-tetrahydrocannabinol of interleukin 2-induced lymphocyte proliferation and lymphokine-activated killer cell activity.

The major psychoactive marijuana component, delta-9-tetrahydrocannabinol (THC), suppressed proliferation of murine spleen cells stimulated with recombinant human interleukin 2 (IL-2) and also suppressed the appearance of the lymphokine-activated killer (LAK) cell phenomenon in IL-2-treated spleen cell preparations. Cell function was depressed in a dose-dependent manner with as little as 2.5 micrograms/ml THC (8 microM). In addition, spleen cells previously stimulated in culture with IL-2 and then incubated with THC for 4 h prior to target cell addition, displayed suppressed cytolytic activity against both YAC-1 and EL-4 tumor targets. Killing of EL 4 cells was suppressed at lower drug doses than the killing of YAC-1 targets. These results suggest that THC can suppress several important functions of IL-2 including clonal expansion of lymphocytes, expansion of killer cell populations and stimulation of killer cell cytotoxic activity.

Animals↗
PubMed1988

Suppression by cannabinoids of a cloned cell line with natural killer cell activity.

Preincubation of a cloned cell line with natural killer (NK) cell activity, as well as splenic mononuclear cells with either delta 9-tetrahydrocannabinol (THC) or 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC) suppressed NK cytolytic activity against YAC-1 target cells in a dose-dependent manner. THC was more inhibitory for cloned cells than 11-OH-THC and suppressed the lytic activity of these cells without reducing cell viability in the concentration range of 5 micrograms/ml (16 microM) to 10 micrograms/ml (32 microM). THC also inhibited proliferation of cloned NK cells, but this inhibitory effect was reversible in that extensive washing of cells following cannabinoid pretreatment eliminated the suppressive effect. Single-cell analysis revealed that THC did not inhibit the binding of cloned NK cells to target cells and further showed that NK cells freshly isolated from mouse spleen were restricted in killing capacity following binding to target cells. Therefore, THC and 11-OH-THC appear to directly inhibit NK cell cytolytic activity in a postbinding stage.

Animals↗
PubMed1988

Altered interleukin production during Friend leukemia virus infection.

Spleen cells from BALB/c mice, infected 14 to 28 days earlier with Friend leukemia virus (FLV), were shown to be inhibited in their ability to produce interleukin 2 (IL-2) when stimulated with mitogen. Likewise, these spleen cell populations failed to respond following mitogenic stimulation or exogenous addition of recombinant IL-2. By contrast, the FLV-infected spleen cell populations produced normal levels of interleukin 1 (IL-1) and thymocytes from FLV-infected mice responded normally to addition of exogenous IL-1. This suggests that FLV infection selectively affects the ability of spleen cells to produce cytokines. Spleen cell populations enriched for T lymphocytes and depleted of tumor cells by density gradient centrifugation in Ficoll were unable to produce IL-2. This indicates that the failure to detect IL-2 in cells from FLV-infected mice was not due to a dilution of T lymphocytes by tumor cells but was a functional inability to produce IL-2. Furthermore, enriched T lymphocytes from FLV-infected mice failed to respond blastogenically to exogenous IL-2. Additional studies indicate that tumor cells, but not macrophages or T lymphocytes from FLV-infected spleens, suppressed the blastogenic response to mitogens and IL-2 production by normal splenic T lymphocytes.

Animals↗
PubMed1988

Drugs of abuse and virus susceptibility.

It is widely recognized that various microorganisms including viruses have immunomodulatory effects and, under appropriate circumstances, may markedly suppress the immune response mechanisms. Cannabinoids present in marijuana also have immunomodulatory effects. In the present studies THC as well as its metabolic product 11-OH THC were studied in regard to their effects in vivo and in vitro on selected parameters of the immune response system known to be important in antiviral resistance, including immunity to retroviruses. Cannabinoids markedly suppressed the ability of murine macrophages to spread on glass (an important functional marker of macrophages) as well as to phagocytize yeast particles. Splenic macrophage cultures treated with the cannabinoids also were deficient in their ability to produce interleukin 1 on appropriate stimulation with bacterial LPS. Spleen cells capable of producing antibody to sheep erythrocytes when stimulated with this antigen in vitro were markedly affected when treated with graded doses of THC or 11-OH THC. Furthermore, the blastogenic responsiveness of normal mouse splenocytes to the T-cell mitogens Con A and PHA as well as the B-cell mitogen E. coli LPS was markedly suppressed by graded concentrations of the cannabinoids in doses that did not affect the viability of the cells. Natural killer cell activity of normal mouse spleen cells was also markedly inhibited by THC and 11-OH THC. Similarly, these cannabinoids suppressed the blastogenic responsiveness and NK activity of human peripheral blood leukocytes from normal individuals. The ability of mouse spleen cells to produce interferon on in vitro stimulation was also suppressed by THC. In addition, injection of THC into mice suppressed blastogenic responsiveness of spleen cells, NK activity, and the production of interferon by lymphoid cells. Thus, it was apparent that these cannabinoids had immunomodulatory effects, both in vivo and in vitro, at noncytotoxic small doses and impaired the ability of the lymphoid cells to express immune function necessary for antiviral resistance.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Effects of T cell growth factor/interleukin II on prothymocytes.

The present report describes evidence to show that interleukin 2 (IL-2), in addition to its well known action as a second signal in mitogenic action on mature T cells, functions as a regulator of both proliferation and maturation of immature T lymphocytes. The present experiments extend previous observations indicating that immature thymocytes (Thy1+, L3T4-, Ly2-) are a target of IL-2 action. IL-2 and thymosin fraction V but not interleukin 1 (IL-1) induce differentiation of prothymocytes (Thy1-, L3T4-, Ly2-) obtained from spleens of nude mice as measured by the acquisition of the Thy 1 marker. IL-2, but not thymosin fraction V and IL-1, modulates the proliferation of this cell population. The data indicate that IL-2 may exert a significant regulatory function in T cell ontogeny.

Animals↗
PubMed1985

Vibrio vulnificus resists phagocytosis in the absence of serum opsonins.

Invasive disease caused by Vibrio vulnificus may result partially from resistance to phagocytic host defense mechanisms. The present studies show that V. vulnificus resists phagocytosis by murine peritoneal macrophages in the absence of serum opsonins and extracellular bacterial products, apparently through the anti-phagocytic properties of the bacterial surface.

Animals↗
PubMed1984

Cell-mediated immune responsiveness to cardiac extracts by peripheral blood leukocytes from patients after myocardial infarction or open-heart surgery.

A microdroplet in vitro procedure measuring migration inhibition was utilized to assess cell-mediated immune reactions by peripheral blood leukocytes from patients after myocardial infarction or cardiac surgery. The antigen preparations were derived from human cardiac tissue. Whereas whole-cell extracts and human myoglobin preparations had little effect on migration, mitochondrial preparations markedly inhibited the migration of blood leukocytes from a majority of the patients. Inhibition of migration appeared to reflect development of cell-mediated immunity to heart antigens after myocardial infarction or surgery. These results extend observations of anticardiac immune development in patients following cardiac injury. Two patients demonstrated a direct relationship between enhanced migration inhibition and clinical disease. It is likely that autoreactive responses to cardiac tissue may be involved and influence subsequent physiological events following initial cardiac infarction or surgery.

Adolescent↗
PubMed1984

Dimethyl sulfoxide-induced inhibition of the immunosuppressive activity of cultured Friend erythroleukemia cells.

Two Friend leukemia virus-induced tumor cell lines lost their immunosuppressive properties in vitro when treated with dimethyl sulfoxide (DMSO), a known cellular differentiation agent. Incubation of the cell lines, GM 979 and GM 86, with DMSO for 4 days or longer, inhibited their ability to suppress the antibody forming capacity of normal murine spleen cells immunized in vitro with sheep red blood cells. Suppression of the inhibitory capability of the tumor cell lines by DMSO was time dependent. Three days incubation caused only slight, if any, inhibition, while a shorter period of treatment had no effect. Inhibition of the immunosuppressive properties of the tumor cell lines was not due to a decrease in tumor cell viability. The development of previously reported metabolic alterations in the treated cells, such as increased hemoglobin synthesis and other physicochemical alterations, paralleled cellular differentiation, and loss of immunosuppressive properties.

Animals↗
PubMed1984

Lymphoblastoid cell-induced suppression of human peripheral blood leukocyte mitogenic responses.

Two lymphoblastoid tumor cell lines, the Burkitt lymphoma derived BJAB cell line which is free of Epstein-Barr virus (EBV) and B95-8 cells, which are marmoset lymphocytes transformed by EBV isolated from an infectious mononucleosis patient, were studied in regards to their effects on the blastogenic responsiveness of normal human peripheral blood leukocytes stimulated in vitro with mitogens. Mitomycin C treated tumor cell suspensions, when cocultured with normal human blood leukocytes, markedly depressed the expected blastogenic responses in vitro to concanavalin A, pokeweed mitogen, and phytohemagglutin. In addition, cell-free sonicates from the cell lines also depressed blastogenic responsiveness of the leukocytes in vitro. Heating the sonicates for 10 min at 100 degrees C markedly diminished the suppressive properties of the sonicates, as did ultraviolet light irradiation. The suppressive activity of the B95-8 sonicates was pelleted by high speed centrifugation as compared to the activity of sonicates derived from the BJAB cells. Further studies are warranted to determine the nature and mechanism of suppression of blastogenic responsiveness of normal human leukocytes by soluble components derived from such lymphoblastoid cell lines.

Animals↗
PubMed1984

Suppression of natural killer cell activity by Friend murine leukemia virus.

BALB/c mice infected with Friend murine leukemia virus (F-MuLV) evinced a decreased natural killer (NK) cell activity to susceptible target cells. This suppression increased as the interval between infection and assay was lengthened. The decrease in NK activity due to F-MuLV infection was partially reversible when spleen cells were pretreated with interferon before the cytolytic assay. The ability of F-MuLV-infected splenocytes to bind to target cells was unaltered, indicating that the defect was in the lytic phase of NK cytolysis. When mixed with uninfected spleen cells, F-MuLV-infected splenocytes suppressed their NK cell activity. This suppression was associated with a nylon wool-adherent cell population in the F-MuLV-infected spleens.

Animals↗
PubMed1983

Cell-mediated immune injury to the heart.

A micro in vitro procedure was utilized to assess cell-mediated immunity of patients following myocardial infarction or cardiac surgery. For this purpose, peripheral blood leukocytes from patients were tested in a microdroplet assay with antigen preparations derived from human cardiac tissue. Whereas whole saline extract and human myoglobin preparations had little effect on the migration of peripheral blood leukocytes in vitro, mitochondrial preparations were markedly effective in inhibiting migration of the leukocytes in the presence of mitochondrial extracts appeared to reflect development of cell mediated immunity to heart antigens after the myocardial infarct or surgery. These results extend the observations that humoral antibody may appear in patient following cardiac injury. The role of either antibody or sensitized lymphoid cells in mediation of post-myocardial infarction or post-cardiotomy syndromes is not clear, but it appears clear that injury to the heart induced auto-reactive responses which may play a role in subsequent pathologic events following the initial cardiac injury.

Adolescent↗
PubMed1983

Influence of viruses on cells of the immune response system.

A wide variety of immune parameters may be influenced in vivo and in vitro during virus infections. Some viruses appear to specifically alter macrophage activity, while other viruses preferentially affect activity of lymphocytes, both B and T cells. There are many mechanisms involved in immune derangement during virus infection, including the possibility that viruses preferentially interact with selected classes of immunocompetent cells. Alternately, some of the events associated with viral derangement of the immune response may be associated with the release or formation of factors by cells infected with a virus which affects other cells of the immune system. Similarly, the development of immune complexes resulting from the interaction of viruses or their components with antibody directed to the virus may influence the immune response, as well as induce other immunopathologic manifestations. Many model systems have been studied, especially those with viruses important to human infection. It is noteworthy that leukemia viruses and, in some cases, other tumor associated viruses may directly alter the immune response, usually before other manifestations of the tumorigenic process is evident. Tumor virus-induced immunomodulation is associated with direct effects of a virus on immunocompetent cells per se as well as the formation of soluble factors induced by the virus infection. These and other considerations indicate that interactions of viruses with the host immune defense system are an important consideration in understanding how virus infection is initiated and progresses, and how such infection affects the host's physiologic activity, including immunocompetence, per se.

Animals↗