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Biomedical subjects

W R Benjamin

Publications and source records attributed to W R Benjamin.

33 records · Page 2Linked to original sources
PubMed1985

Different susceptibilities to cyclosporin A of the mitogenic and potentiating activities of interleukins.

A dissociation was observed between the mitogenic and potentiating activities of interleukins (ILs)-1 or -2 in murine thymocyte cultures treated with drugs. The direct mitogenic effects of the ILs were unaffected by cyclosporin A (CsA) at concentrations which abolished the potentiating activities of these mediators, i.e. their synergy with lectins. Conversely to CsA, dexamethasone was more inhibitory to the mitogenic activity of the ILs than to their synergistic reactions with the lectins. The resistance to CsA of the mitogenic activity of IL-1 was unexpected since this response is assumed to be mediated by newly formed IL-2 and CsA inhibits IL-2 production. This resistance was further tested by coculturing thymocytes with the IL-2-dependent CT6 cells; net gains of thymidine uptake by the cocultures were attributed to IL-2 release. Such net gains were observed in cocultures stimulated with IL-1 alone and were relatively resistant to CsA. On the other hand, net gains stimulated by mitogenic lectins, alone or with IL-1, were eliminated by CsA. These results support the notion that IL-1 direct activity on thymocytes is mediated by newly released IL-2 and show that this IL-1 activity is unusual in being resistant to CsA. Low levels of protection against CsA were also observed in cultures potentiated by IL-1: lymphocytes stimulated by lectins or antigens and IL-1 were inhibited by CsA less than lymphocytes stimulated without IL-1. Yet, this partial protection by IL-1 was achieved only at CsA concentrations about 100 fold lower than those resisted by thymocytes directly stimulated by IL-1.

Adjuvants, Immunologic↗
PubMed1985

Resistance to adenovirus infection after administration of Bordetella pertussis vaccine in mice.

Treatment of mice with Bordetella pertussis vaccine rendered mice resistant to mouse adenovirus infection. The resistant state took at least 5 days to develop, and susceptibility returned to a portion of the test population 35 days after treatment. Transient resistance developed in congenitally athymic mice also. Treatment with a dose of 25 micrograms (dry weight) of B. pertussis vaccine protected approximately 50% of the test population. Vaccines prepared from several different strains of B. pertussis were capable of inducing resistance, and the induction of resistance was not dependent on the mouse strain used for testing. Cross-reacting antibodies capable of neutralizing the virus or protecting against a challenging infection were not induced by treatment with B. pertussis vaccine.

Adenoviridae Infections↗
PubMed1984

Differential effects of positive and negative proliferative stimuli on murine cytolytic and helper T-cell clones.

Studies were performed to determine whether substances could be identified which exhibited differential regulatory effects--either positive or negative--on the growth of murine alloreactive cytolytic (Tc) and helper (Th) cloned T-cell lines. The following lines of evidence suggested that Tc and Th proliferate in response to the same growth factor (GF). (1) When GF-containing fluids from cultures of phorbol myristic acetate (PMA)-activated EL4 thymoma were fractionated by a variety of biochemical techniques. Tc and Th eluted together. (2) Absorption of GF-containing supernatants with either cloned Tc or cloned Th depleted GF activity for each to a similar extent, and GF eluted from either Tc or Th to which it had adsorbed supported the proliferation of Tc and Th equally well. (3) Lectin-depleted supernatants from cultures of concanavalin A (Con A)-activated Th stimulated the proliferation of Th as well as Tc. (4) Recombinant human interleukin (IL-2) supported the growth of Tc and Th with equal efficiency. On the other hand, the following observations indicated that Tc and Th differed in their responses to inhibitors of GF-driven proliferation. (1) Con A at greater than or equal to 0.3 micrograms/ml inhibited the GF-driven proliferation of each of three Th lines but not either of two Tc lines. To the contrary, Con A enhanced GF-dependent proliferation of Tc. (2) Like Con A, allogeneic splenocytes selectively depressed GF-driven proliferation of Th but not Tc. (3) A substance generated during the acid elution of GF from cells, possibly a modified fetal calf serum component, greatly reduced the GF-driven proliferation of Tc but not Th. These results suggest that differential control of the proliferation of Tc and Th in cellular immune responses may be achieved via negative regulatory signals and raise the possibility that substances which can selectively depress the proliferation of specific T-cell subsets might be found which would be of therapeutic value.

Animals↗
PubMed1983

Activation of macrophages for microbicidal and tumoricidal effector functions by soluble factors from EL-4, a continuous T cell line.

Macrophages treated with culture fluids from EL-4 cells, a continuous T cell line, were activated to kill mKSA-TU-5 fibrosarcoma cells, amastigotes of Leishmania tropica, and schistosomula of Schistosoma mansoni. Active EL-4 factors eluted from Sephadex G-100 in two distinct regions: molecular weight 45,000 (activities induced killing of unrelated intracellular and extracellular targets) and molecular weight 23,000 (activities induced killing of extracellular targets only). These results confirm heterogeneity among activation signals for the induction of macrophage microbicidal and tumoricidal activities. Factors that induced cytocidal activity against extracellular tumor cells and schistosomula were distinct from those that induced destruction of intracellular amastigotes.

Animals↗
PubMed1983

The cellular basis for immune interferon production in autoimmune MRL-Ipr/Ipr mice.

Disturbances in immune interferon (IFN gamma) activity have been implicated in the development of human systemic lupus erythematosus (SLE) and the spontaneous disease sustained by autoimmune-prone mice. We therefore investigated the cellular basis for IFN gamma production in MRL-Ipr/Ipr mice and examined the relationship between synthesis of interleukin 2 (IL 2) and IFN gamma. In vitro IL 2 and IFN gamma production in 3 to 6-mo-old, autoimmune MRL-Ipr/Ipr and MRL-+/+ mice was compared with that seen in age- and sex-matched, immunologically normal CBA/J mice. 5 X 10(6) spleen cells were pulsed with 5 micrograms of concanavalin A (Con A), and the cellfree supernatant was assayed for IL 2 and IFN gamma activity at various times up to 72 hr. We found that peak levels of IL 2 in MRL mice were less than 10% of those in the CBA/J. Yet, production of IFN gamma by cells from the autoimmune and normal strains was quite comparable. The addition of murine IL 2 to optimally Con A-stimulated cells from the MRL-Ipr/Ipr or normal mice did not affect the subsequent peak production of IFN gamma. Although the primary producers of IFN gamma in cultures of normal mice bear the Lyt-2+ phenotype, the Lyt-1+2- T-cell subset was found to be the principal source of IFN gamma in the aged MRL-Ipr/Ipr. These data suggest that Lyt-1+ cells from MRL-Ipr/Ipr mice may be differentially responsive to the signal delivered by the same mitogenic lectin with respect to lymphokine production and may indicate a distorted commitment of such cells toward production of IFN gamma and repression of IL 2 synthesis. The relationship between hypoproduction of IL 2, this usual source of IFN gamma, and the autoimmune disease sustained by MRL-Ipr/Ipr mice remains unclear.

Animals↗
PubMed1982

Production of immune interferon by an interleukin 2-independent murine T cell line.

An interleukin 2-independent murine T cell line (BFS) was isolated that produced immune interferon after stimulation with phorbol 12-myristate 13-acetate. The BFS cell line did not produce detectable levels of interleukin 1, interleukin 2, B cell growth factor, macrophage-granulocyte colony-stimulating factor, macrophage-activating factor, or T cell replacing factor. Maximal interferon was induced 48 hr after stimulation with phorbol myristate acetate at 10-100 ng/ml. Production of interferon by phorbol myristate acetate-stimulated BFS cell cultures was synergistically increased by the addition of EL4 thymoma cell culture supernatants. BFS-derived interferon activity was sensitive to pH 2 treatment and was neutralized with antiserum to immune interferon but was resistant to heating at 56 degrees C and to treatment with antiserum to type I interferon. In addition, the interferon activity was sensitive to trypsin but resistant to RNase. BFS-derived interferon had an apparent molecular weight of 48,000 and a pI of 5.5-6.0. Each of these properties is consistent with the conclusion that the BFS cell line produces immune interferon after stimulation with phorbol myristate acetate.

Animals↗
PubMed1982

Macrophage activation for tumor cytotoxicity: induction of macrophage tumoricidal activity by lymphokines from EL-4, a continuous T cell line.

Supernatant culture fluids from a phorbol myristate acetate (PMA) stimulated variant of the murine EL-4 thymoma cell line activated inflammatory macrophages for nonspecific tumoricidal activity in vitro; active supernatants fluids were not directly toxic to tumor target cells in the absence of macrophages. Macrophages treated with culture fluids of unstimulated and concanavalin A-stimulated EL-4 or PMA-stimulated cells derived from any of ten other continuous T cell lines were not cytotoxic. The titer of activity in lymphokines from PMA-stimulated EL-4 was similar to that from antigen-stimulated spleen cell cultures. Spleen cell and EL-4 derived activities were both retained within a dialysis membrane and destroyed by heating at 100 degrees C for 15 min. However, unlike the activity in spleen cell-derived LK, activity in EL-4 culture fluids was stable to dialysis against pH 2 buffer. Further physicochemical characterization of the EL-4 activity showed two different factors that activated macrophages for cytotoxicity: one was indistinguishable from gamma interferon (IFN) (antiviral activity, 50,000 m.w., pI 4.2 to 6.0, pH 2 labile and neutralized by anti-gamma IFN serum); the other was clearly distinct (no antiviral activity, 23,000 m.w., pH 2 stable and unaffected by anti-gamma IFN serum). These results suggest that the EL-4 cell line may produce one or more of the macrophage activation factors present in spleen cell-derived lymphokines.

Animals↗
PubMed1981

Inhibition of yeast phagocytosis and cell spreading by glucocorticoids in cultures of resident murine peritoneal macrophages.

This study was initiated to determine whether the inhibition of phagocytosis and cell spreading in cortisol-treated cultures of resident murine peritoneal macrophages are glucocorticoid-directed responses. Phagocytosis of heat-killed Saccharomyces cerevisiae and cell spreading were measured in control and steroid-treated macrophage cultures over 6 days. When the cultures were exposed to testosterone, progesterone, or epicortisol, phagocytosis and cell spreading were similar to controls. In contrast, both macrophage functions were inhibited significantly in cultures treated with cortisol, methylprednisolone, dexamethasone, and triamcinolone acetonide. In addition, the rate of phagocytosis was retarded and phagocytic indices (i.e., yeast particle number/cell) were reduced in glucocorticoid-treated cultures. Dose-response studies with dexamethasone demonstrated that the ED50 for the inhibitory effect on phagocytosis was 20 nM. These results indicate that the inhibition of yeast phagocytosis and cell spreading in the steroid-treated cultures are specific glucocorticoid-directed responses.

Animals↗
PubMed1980

Evaluation of solid-phase immunofluorescence for quantitation of antibodies to herpes simplex virus and cytomegalovirus.

A recently developed semiautomated technique based on solid-phase immunofluorescence (FIAX) was compared with complement fixation for the determination of antibody levels to herpes simplex virus and cytomegalovorus in human serum samples. The results demonstrated that the FIAX method was in aggreement with the complement fixation technique for 97% of the serum samples tested. Reproducible titers were obtained from multiple FIAX determinations of representative sera within the same experimental run and between separate experimental runs. However, variability was rather high for patient sera with low (less than or equal to 1:5) antibody levels to cytomegalovirus. Hence, the results obtained by the FIAX technique were reproducible, and the FIAX system was as sensitive as complement fixation for the determination of antibody levels to herpes simplex virus and cytomegalovirus.

Antibodies, Viral↗
PubMed1978

Characterization of mouse peritoneal exudate and associated leukocyte adherence inhibitory activity after intraperitoneal injection of either Bordetella pertussis or Corynebacterium parvum vaccines.

Bordetella pertussis and Corynebacterium parvum are commonly used immunopotentiating agents. To explore the inflammatory environment induced by these agents, the peritoneal exudate response in mice following intraperitoneal injection of B. pertussis (PV) and C. parvum (CV) vaccines was investigated. The PV-induced exudate isolated by lavage was characterized by an early neutrophil influx followed by enhanced accumulation of mononuclear cells and fluid protein. The CV exudate was principally mononuclear in nature and displayed fewer numbers of cells and less fluid protein. Both vaccines also enhanced the leukocyte adherence inhibitory activity (LAIA) of peritoneal fluid as measured in vitro. The development of exudate LAIA was T lymphocyte independent. A similar LAIA was demonstrated in nonimmune mouse plasma and serum. Exudate fluid and serum LAIA were heat stable and trypsin sensitive. These studies suggest that significant differences exist in the composition of the local tissue environment following PV and CV injection and that exudate LAIA is serum derived. Further studies in this direction should result in a better understanding of the ways in which inflammatory cells and fluid substances affect lymphocyte-macrophage interaction subsequent to adjuvant administration.

Animals↗