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L S Soderberg

Publications and source records attributed to L S Soderberg.

53 records · Page 3Linked to original sources

Susceptibility to reinfection after a primary chlamydial genital infection.

Female guinea pigs which had been infected genitally with the agent of guinea pig inclusion conjunctivitis were challenged at various times after infection with fresh inocula to determine the duration of immunity resulting from the primary infection. At 30 days after infection, most guinea pigs were resistant to reinfection, as indicated by the inability to isolate chlamydiae from cervical swabs. However, at 77, 155, and 294 days, all animals became reinfected, although the course of the infection was abbreviated and of lower intensity. When various immune parameters were examined, a decrease in antibodies in both serum (immunoglobulin G [( IgG]) and genital secretions (IgA, IgG) was observed after 30 days. A decrease in antibodies to the major outer membrane protein and an 84K component was noted in serum. In genital secretions, IgA antibodies to all major chlamydial components declined markedly after 30 days. Cell-mediated immunity as measured by proliferation of peripheral blood lymphocytes to guinea pig inclusion conjunctivitis antigen also was at a peak response 30 days after infection and decreased thereafter. Thus, loss of complete immunity could not be associated with a particular immune parameter. When genital secretions were examined 14 days after the challenge infection, IgA antibody levels to the lipopolysaccharide and 61K protein components had increased in intensity, whereas other antibodies were relatively low. In addition, complete immunity to a third infection was not increased in duration when animals had recovered from two previous genital infections.

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Copper(II)2(3,5-diisopropylsalicylate)4 stimulates hemopoiesis in normal and irradiated mice.

We have previously reported that copper(II)2(3,5-diisopropylsalicylate)4 (Cu-DIPS) significantly increased the survival rate of mice exposed to lethal irradiation. To examine whether Cu-DIPS affected hemopoietic activity, groups of mice were treated with Cu-DIPS or vehicle and assayed for in vitro interleukin 3 (IL-3)-dependent colony-forming units (CFU-C) and for committed progenitor granulocyte-macrophage CFU (GM-CFU). Cu-DIPS increased the number of splenic IL-3 CFU-C by five- to sixfold 7 days after treatment and splenic GM-CFU by 12-fold on day 24. These increases were accompanied by a 50% increase in spleen weight. Bone marrow IL-3 CFU-C and GM-CFU were not affected at 7 or 14 days after treatment, but were somewhat depressed at 24 days. In irradiated (8.0 Gy) mice treated with Cu-DIPS or vehicle, splenic IL-3 CFU-C and GM-CFU were undetectable 7 days after irradiation, but recovered more rapidly in Cu-DIPS-treated mice. By 24 days splenic IL-3 CFU-C in Cu-DIPS-treated mice recovered to 150% of normal (unirradiated) values and GM-CFU recovered to 270% of normal, whereas irradiated control values remained at 25% and 7%, respectively. The recovery of bone marrow hemopoiesis was slower than spleen, but 42 days after irradiation Cu-DIPS-treated mice had higher levels of bone marrow IL-3 CFU-C (eightfold) and GM-CFU (4.6-fold) than vehicle-treated mice. Cu-DIPS stimulated sixfold increases in renewable, pluripotent stem cells as measured by the in vivo assay of endogenous colony-forming units (CFU-Se).

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The effect of in utero exposure to hexachlorobenzene on the developing immune response of BALB/c mice.

BALB/c mice were exposed to 0.0, 0.5 and 5.0 mg/kg maternal body weight hexachlorobenzene (HCB) throughout gestation by daily per os dosing of the females. At 45 days of age selected immune functions of the offspring were assessed. The delayed-type hypersensitivity (DTH) response to oxazolone was severely depressed in animals exposed to either 0.5 or 5.0 mg/kg HCB, however, only those animals exposed to 5.0 mg/kg HCB showed a significant decrease in their mixed lymphocyte response (MLR) levels. The ability of isolated spleen cells to undergo a blastogenic response to concanavalin A (ConA), phytohemagglutinin (PHA) and lipopolysaccharide (LPS) showed no significant changes due to HCB exposure. Similarly, no significant difference in the induction of direct hemolytic plaque-forming cells was seen. A significant increase in the relative distribution of splenic T cells and a significant decrease in splenic B cells was measured in the offspring of HCB-treated females. These results suggest that HCB is capable of affecting the development or maturation of the immune response in mice, perhaps at the T cell level.

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Copper(II)(3,5-diisopropylsalicylate)2 accelerates recovery of B and T cell reactivity following irradiation.

Copper(II)(3,5-diisopropylsalicylate)2 (Cu-DIPS), administered subcutaneously to mice at 80 mg/kg body weight, had marked radioprotective activity. Given 3 h before exposure to 8.0 Gy (800 rad) irradiation, Cu-DIPS increased the 42-day survival from 40% to 86%. Seven days after exposure to 8.0 Gy, there were severe reductions in spleen weight (73%) and cellularity (98%) in both Cu-DIPS- and vehicle-treated mice. Viable spleen cells collected 7 days after irradiation were totally unresponsive to mitogenic or antigenic stimulation regardless of Cu-DIPS or vehicle treatment, suggesting that Cu-DIPS did not prevent radiation-induced damage to mature lymphocytes. At 14 days, when Cu-DIPS-treated mice started to show improved survival over vehicle-treated mice, spleen weights and cellularity were 2.5- and 3.5-fold higher, respectively, in Cu-DIPS-treated mice. Treatment with Cu-DIPS not only enhanced splenic repopulation, but also accelerated the reappearance of both B and T cell reactivities. Spleen cell responsiveness to the B cell mitogen, lipopolysaccharide (LPS), and the T cell mitogen, concanavalin A (Con A), regenerated significantly faster in Cu-DIPS-treated mice. Cu-DIPS also significantly accelerated the regeneration of T-dependent antibody induction. Based on these assays of immunocompetence, Cu-DIPS-treated mice had, on average, a seven-fold greater capacity to respond to immune stimulation than vehicle-treated mice 24 days after irradiation.

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Rabbit bone marrow suppressor cells block the production or release of a soluble bone marrow growth factor.

Fc gamma-receptor (Fc gamma R)-bearing cells from normal rabbit bone marrow suppressed the constitutive proliferation rates of the remaining, Fc gamma R-, cells. In the absence of the suppressive influences of Fc gamma R+ cells, cells in the Fc gamma R- population spontaneously elaborated a soluble growth factor (GF) which induced the proliferation of unseparated bone marrow cells. To examine regulation by Fc gamma R+ bone marrow cells, graded numbers of the Fc gamma R+ cells were mixed with constant numbers of the FcR- cells. At 24 hr, supernates were collected and tested for GF activity. The Fc gamma R+ suppressor cells efficiently and in a dose-dependent fashion blocked GF production or release. The GF was nondialyzable and relatively heat stable. Supernates with GF activity also had colony-stimulating factor activity, but were negative in assays modified from murine interleukin 1 (IL-1) and IL-2 assays. Regulation of GF production or release represents a new function for bone marrow suppressor cells.

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The effect of prenatal chlordane exposure on the delayed hypersensitivity response of BALB/c mice.

Previous studies in our laboratory have indicated that in utero chlordane exposure caused a significant enhancement in the survival of the offspring to influenza virus infection. Further studies, reported here, show that the non-specific delayed type hypersensitivity (DTH) response to oxazolone at 100 days of age, but not at 30 days of age, was significantly depressed. In contrast, the Con A-induced blastogenic response of spleen cells from chlordane-treated offspring was not depressed and was, in fact, significantly enhanced. However, neither the response to PHA nor to LPS mitogens was significantly altered. In utero exposure to chlordane significantly depressed the mixed lymphocyte reactivity (MLR) of spleen cells from male offspring, whereas females showed no significant alteration of MLR. The significant depression of the DTH and MLR responses supports our previous reports of enhanced survival of influenza virus infection following in utero exposure to chlordane, since active DTH contributes to the pathology of influenza virus infection in mice. The normal or enhanced T-cell mitogen response suggested that the chlordane-induced depression of DTH and MLR was not due to overt toxicity to T-cells.

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Influenza type A virus infection of mice exposed in utero to chlordane; survival and antibody studies.

Previous studies carried out by others have shown that in utero exposure of mice to chlordane effects a significant depression of cell-mediated immunity (CMI) at 100 days of life without adversely affecting the humoral immune system. In the studies reported herein we assessed the effect of in utero exposure to various doses of chlordane on the response of 38-day-old mice to influenza type A virus infection in terms of relative levels of mortality, mean day of death, and the levels of antiviral antibody in the primary and secondary immune response to the virus. In utero exposure to chlordane effected enhanced survival to influenza type A virus infection relative to mock-treated animals. No significant differences were noted in the mean day of death of chlordane-treated and mock-treated mice. A significant enhancement in the levels of antiviral antibody was noted in the chlordane-treated female mice but not male mice in both the primary and secondary immune response to the virus.

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The effect of prenatal chlordane exposure on specific anti-influenza cell-mediated immunity.

Previous studies in our laboratory have documented that in utero chlordane exposure caused a significant enhancement in the survival of the offspring to influenza A virus infection, and a depressed delayed type hypersensitivity (DTH) response to oxazolone. To correlate these 2 effects, we assayed influenza A virus-specific DTH response, and found that it was significantly decreased in chlordane-treated offspring. Virus-specific T-cell blastogenesis was also assayed in chlordane-treated animals. No significant differences due to the chlordane treatment were found in virus-specific T-cell blastogenesis, suggesting that the DTH depression did not result from a paucity of antigen-reactive T-cells. To determine whether enhanced survival was due, in part, to the effects of chlordane on virus replication, rather than on immunological alteration alone, the kinetics of influenza virus replication in the lungs of chlordane- and vehicle-treated animals were determined. In utero chlordane treatment caused no significant differences in in vivo virus replication. These data suggest that increased survival was due to a decrease in virus-specific DTH and its associated pathology.

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Chronic chlamydial genital infection in congenitally athymic nude mice.

Congenitally athymic nude mice and their heterozygous counterparts were inoculated intravaginally with the chlamydial agent of mouse pneumonitis, a Chlamydia trachomatis biovar. Heterozygous mice resolved their infections in 20 days, whereas nude mice developed chronic infections which lasted at least 265 days and did not resolve within the time course of the experiments. Heterozygous mice produced high levels of antibody in both serum and secretions in contrast to nude mice, which produced very low levels of antibody in serum alone.

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Regulation of constitutive bone marrow cell proliferation by bone marrow suppressor cells.

Bone marrow (BM) cells have previously been shown to suppress specific immune responses of cells from peripheral lymphoid organs. The present report describes a suppressor cell present in normal rabbit BM, which regulated the constitutive proliferation of other BM cells. The suppressor cells were Fc gamma-receptor-positive (Fc gamma R+) complement-receptor-negative, and nonadherent or weakly adherent. Similar suppressive activity was not detected among rabbit spleen cells. Removal of Fc gamma R+ suppressor cells allowed greater than 10-fold increases in the proliferation of Fc gamma R- BM cells. Addition of Fc gamma R+ BM cells to Fc gamma R- cells efficiently blocked proliferation. The suppressor cells acted by inhibiting the elaboration of a soluble growth-promoting factor by cells in the Fc gamma R- population. The growth-promoting factor enhanced proliferation of unseparated rabbit BM cells and peripheral blood mononuclear cells.

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Differential activities of rabbit bone marrow suppressor cells.

A population of nonadherent Fc gamma-receptor-bearing (Fc gamma R+) suppressor cells in normal rabbit bone marrow (BM) which inhibited the constitutive proliferation of other BM cells has been previously described. Suppression was by blocking the release of a soluble growth-promoting factor. In the present report, it was found that the Fc gamma R+ BM suppressor cells, which were suppressive to background proliferation, were not suppressive to lymphocyte activation by immune complexes (IC). Adherent BM cells showed suppressive activity toward IC stimulation, but none toward constitutive BM proliferation. IC-induced proliferation was enhanced by the soluble growth factor, but only in the absence of adherent cells. Adherent cells did not affect growth factor enhancement of constitutive proliferation, suggesting that different cell populations were affected. Depletion of the Fc gamma R+ suppressor cells promoted growth of cells which subsequently developed Fc gamma R+, increasing the possibility of interaction with IC, which also preferentially induced Fc gamma R+ cells.

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T cells and the anti-trinitrophenyl antibody response to fetal calf serum and 2-mercaptoethanol.

Unprimed murine lymphocytes maintained in culture medium containing fetal calf serum (FCS) and 2-mercaptoethanol (2-ME) developed very high levels of anti-trinitrophenyl (TNP) plaque forming cells (PFC). Both FCS and 2-ME contributed to the response. The development of anti-TNP PFC during culture was accompanied by a 10-fold expansion in the number of immunoglobulin-secreting cells, indicating polyclonal stimulation. However, the number of anti-TNP PFC was disproportionately high and not accompanied by a similar increase in plaques specific for sheep red blood cells. The TNP-specific plaques were not artifacts of the plaque assay since they were 98% inhibited by specific antigen. The in vitro induction of anti-TNP PFC by FCS and 2-ME was common to a number of mouse strains, although some genetic variation occurred. Nylon-wool-separated B cells, nude mouse spleen cells, and bone marrow cells all produced high levels of anti-TNP after culture with medium containing FCS and 2-ME. The addition of T cells to B-cell cultures increased the numbers of anti-TNP PFC by 1.5- to 2.5-fold. The presence of a TNP-cross-reacting antigen in FCS probably contributed to the unexpectedly high anti-TNP response. The response to the antigen in FCS was potentiated by the enhancing activity of 2-ME.

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Antigen-antibody complex binding and cell interaction in stimulating normal rabbit lymphocytes.

Complexes of antigen with specific antibody have been shown to enhance or suppress the specific antibody response in vivo. In vitro, antigen-antibody (Ag-Ab) complexes prepared in a slight antigen excess with rabbit antibody induced proliferation of unprimed rabbit lymphocytes. The Ag-Ab stimulated cells from a number of different normal lymphoid organs, including peripheral blood, bone marrow, spleen, and lymph node, but not thymus. Cells exposed to Ag-Ab for 1 hr and washed, bound Ag-Ab through Fc and complement receptors (CR), but were not induced to proliferate unless additional Ag-Ab was added. Specific antigen, which was otherwise unstimulatory, interacted with Ag-Ab-coated cells to activate them, probably through the cross-linking of membrane-bound ligands. Proliferation stimulated by Ag-Ab involved the interaction of three bone marrow cell subpopulations; a macrophage-enriched, a B-cell-enriched, and an mIgM- cell-enriched population. The separated subpopulations were poorly responsive to Ag-Ab stimulation, even though Ag-Ab bound to cells in each of the populations. Low levels of responsiveness to Ag-Ab also resulted when any two of the three subpopulations were combined. Only when all three subpopulations were mixed, was stimulation equivalent to the levels of stimulation reached by unseparated cells.

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Fetal calf serum and 2-mercaptoethanol induce anti-trinitrophenyl antibody production: II. Preferential stimulation of B cells in culture.

Fetal calf serum (FCS) and 2-mercaptoethanol (2-ME) are commonly used in culture media because they enhance lymphocyte responsiveness. We had previously reported that FCS and 2-ME generate high antitrinitrophenyl (TNP) antibody plaque-forming cell responses in unprimed murine spleen cells without added antigen. This was due in part to a component in FCS, which was antigenically cross-reactive with TNP. In the present report, we studied the mitogenic activity of FCS and 2-ME, which also contributed to the high anti-TNP response. Such mitogenic activity could not be replaced by B- or T-cell mitogens. Both FCS and 2-ME were required for the mitogenic activity, which was directed primarily at B cells. Purified T cells and spleen cells from B-cell-depleted mice were unresponsive to FCS and 2-ME stimulation. The mitogenic activity was not due to lipopolysaccharide (LPS) contamination of FCS, since cells of the LPS-unresponsive mouse strain, C3H/HeJ, were stimulated by FCS and 2-ME.

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Complement-dependent stimulation of normal lymphocytes by immune complexes.

Normal rabbit lymphocytes were stimulated to proliferate in vitro by antibody-antigen complexes. Stimulation was dependent upon C activity. Heat-inactivation or zymosan-treatment of the serum used in culture caused a 75 to 100% loss of responsiveness to the complexes. Serum-free culture or cultures with less than 1% serum supported only low levels of stimulation, but responsiveness reappeared proportionally with increased serum concentration. The low level dose-dependent responses seen in the absence of active C may have been due to C carried over with the cells or to stimulation independent of C. Aggregated rabbit gamma-globulin tested over a broad dose range failed to stimulate normal lymphocytes more than minimally whether or not C was present. Stimulation with immune complexes was sustained by C4-deficient guinea pig serum, indicating participation of the alternative C pathway. Normal rabbit lymphocytes from peripheral blood, bone marrow, spleen, and lymph node proliferated in response to rabbit antibody-antigen complexes. Normal thymocytes were consistently unresponsive to the complexes.

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Ribonucleic acid synthesis in normal and immune macrophages after antigenic stimulus.

Macrophage ribonucleic acid (RNA) synthesis is an important metabolic process intimately related to the function of these cells. Mouse peritoneal macrophage RNA was extracted with phenol in the presence of bentonite and electrophoresed on composite agarose-polyacrylamide gels. The pulse-chase technique was used to follow the precursor relationships in macrophage ribosomal RNA (rRNA) maturation. The rRNA species at 18S and 28S appeared at 15 and 45 min, respectively, after RNA synthesis was halted. Their appearance corresponded closely to decreases in the rRNA precursors at 45S, 36S, and 34S. Studies of RNA methylation aided in confirming the identity of these ribosomal species. Unmethylated RNA species appeared as messenger RNA between 5S and 15S, and at about 55S probably represented heterodisperse nuclear RNA. When normal macrophages were incubated with heat-killed Salmonella enteritidis, an acceleration in the maturation of RNA was observed. The accelerated maturation was indicated by the earlier appearance of 28S rRNA and the more rapid development of an equilibrium state, where further labeling did not change the RNA profile. In macrophage RNA from mice immunized with S. enteritidis, rRNA species appeared rapidly but did not accumulate to the same extent as observed for normal macrophages. Precursor rRNA and other RNA species developed as usual, suggesting specific degradation of mature rRNA. Such rRNA wastage could indicate a mechanism controlling ribosome assembly in the non-proliferating activated macrophage. The pattern of RNA synthesis in immune macrophages was essentially unchanged by the presence of heat-killed S. enteritidis in vitro.

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