Suppression of reaginic antibody (IgE) formation in mice by treatment with anti-mu antiserum.

Neonatally initiated injection of anti-mu antiserum in mice has been shown to suppress the formation of reaginic antibodies in response to infection with the intestinal nematode, Nippostrongylus brasiliensis. This observation supports the hypothesis that IgE-producing cells arise from IgM-bearing precursors.

Maintenance of skin xenografts of widely divergent phylogenetic origin of congenitally athymic (nude) mice.

Congenitally athymic (nude) mice accepted for their lifetime intact skin grafts from distantly related mammals (cat, human) and birds (chicken). They also failed to immunologically reject skin grafts from reptiles (lizards) and amphibians (tree frog), although the skin in these grafts underwent varying degrees of disorganization. A definitive role for the thymic defect in this failure to reject xenografts was established by showing that thymus implantation into nude mice enabled them to reject such foreign skin.

Regulation of the antibody response to type 3 pneumococcal polysaccharide. I. Nature of regulatory cells.

The effect of treatment with antilymphocyte serum (ALS) on the magnitude of the plaque-forming cell (PFC) response to Type III pneumococcal polysaccharide (SSS-III) was assessed in athymic nude mice and thymus-bearing littermate controls. Without ALS treatment, the PFC response was slightly higher in nude than in control mice. Treatment with ALS had no effect on the response of nude mice; however, considerable enhancement was noted in thymus-bearing controls. Such enhancement was ALS dose-dependent and demonstrable under conditions in which there was substantial inactivation of thymic-derived "helper" cells required for an antibody response to erythrocyte antigens. These findings suggest that amplifier and suppressor cells, which have been reported to regulate the magnitude of the antibody response to SSS-III, represent populations of thymic-derived cells (T cells) that are not present in nude mice. The activities of "helper" T cells and regulatory T cells appear to be independent of one another and mediated by separate subpopulations of T cells.

Differential recovery of antibody production potential after sublethal, whole-body irradiation of mice.

Mice were given single injections of sheep erythrocytes (SE) or polyvinylpyrrolidone (PVP) at various times after sublethal, whole-body irradiation (550 rad 60CO) and direct, antigen-specific, plaque-forming cell (PFC) responses were quantified. Irradiated mice did not respond to SE or PVP when immunized 15 d postirradiation (PI); by day 30 PI, the responses by irradiated mice were 40-126% of normal to SE and 3-38% of normal to PVP. The impaired recovery after irradiation of immune responses to PVP was not due to altered antigen dose requirements or altered time of peak PFC response and occurred after irradiation of mice by doses as low as 200 rad. Both athymic and euthymic mice had impaired responses to PVP after whole-body irradiation. The impaired response of irradiated mice to PVP was repaired by adoptive transfer of normal bone marrow, fetal liver, or spleen cells and also by spleen cell preparations enriched in Ig+ cells but not by spleen cell preparations enriched in Thy.1+ or Ig- cells. With the aid of additional antigens it was observed that by day 30 PI, mice had recovered ability to respond to the T-cell-dependent antigen SE and the T-cell-independent type-1 antigens 2,4,6-trinitrophenyl-Brucella abortus and butanol-extracted bacterial lipopolysaccharide, but at that time they gave impaired responses to the T-cell-independent type-2 antigens PVP, type III pneumococcal polysaccharide, and phenol-extracted bacterial lipopolysaccharide; they had an immune response pattern similar to that of CBA/N mice having an X-linked immunodeficiency.

Immunosuppression in mouse trypanosomiasis: inhibition of secondary antibody responses is dependent on the time of antigen priming.

Trypanosoma musculi-induced immunosuppression was examined in both congenitally athymic (nude) mice and their phenotypically normal, euthymic littermates using T-independent (polyvinylpyrrolidone = PVP) and T-dependent (sheep erythrocyte = SE) antigens. T. musculi-infected nude mice had significantly diminished direct (IgM) plaque-forming cell (PFC) responses to PVP. In euthymic mice, T. musculi parasitemia significantly inhibited the direct PFC response to both PVP and SE. Trypanosoma musculi-infected euthymic mice had significantly diminished indirect (IgG) SE-specific PFC responses if priming occurred during parasitemia; however, T. musculi parasitemia did not significantly decrease indirect SE-specific PFC responses in euthymic mice if the mice were primed before infection.

Systemic anaphylaxis in mast-cell-deficient mice of W/Wv and Sl/Sld genotypes.

Active systemic anaphylaxis was induced in mast-cell-deficient mice of W/Wv and Sl/Sld genotypes. The mast-cell-deficient mice were successfully sensitized either by an intraperitoneal injection of chicken gamma-globulin (C gamma G) mixed with adjuvant, alum and saline extract of Bordetella pertussis, or by an intravenous injection of C gamma G alone. Sensitized mice showed signs of systemic anaphylaxis and died after one or more intravenous challenge injections of C gamma G. These studies show that active systemic anaphylaxis can occur in mast-cell-deficient mice and suggest that cells other than mast cells may release adequate mediators to support systemic anaphylaxis.

Immune and mitogenic responses by BALB/c, C3H/HeJ, and nude mice to Brucella abortus bacterin and lipopolysaccharide.

The immunogenic and mitogenic properties of Brucella abortus 1119-3 bacterin (BA) and biologically active B. abortus lipopolysaccharide (BA-LPS) were studied using normal and athymic (nude) BALB/c and C3H/HeJ mice. Although BA stimulated 2-mercaptoethanol-sensitive (2-ME-S) primary and secondary antibody responses in all mice, nude mice, in contrast to normal BALB/c and C3H/HeJ mice, did not make substantial 2-mercaptoethanol-resistant (2-ME-R) antibody responses. Similarly, all mice injected with BA-LPS made 2-ME-S primary responses, and the secondary response of thymus-bearing mice contained a substantial 2-ME-R component. Collectively, these observations suggest that although both BA and BA-LPS can stimulate thymus-independent 2-ME-S antibody synthesis, thymus-derived cells are required for optimal immune responses containing a 2-ME-R component. The antibody responses of normal BALB/c and C3H/HeJ mice to BA and BA-LPS were qualitatively and quantitatively similar. Both BA and BA-LPS were mitogenic for spleen cells from normal and nude BALB/c and C3H/HeJ mice but not for thymus cells from normal BALB/c or C3H/HeJ mice, suggesting that both preparations are B-cell mitogens.

Immunological responses of mice to lipopolysaccharide: lack of secondary responsiveness by C3H/HeJ mice.

Mice of the C3H/HeJ strain, which were unresponsive to the biological effects of bacterial lipopolysaccharide (LPS), could not be induced to make specific secondary immunological responses to LPS; they responded to two doses of LPS with a primary response. This lack of secondary responsiveness by C3H/HeJ mice was due to a defect in a single, autosomal, dominant gene. Thus, further evidence was provided that an intact second immunological signal and responsiveness thereto were required to trigger secondary antibody responses in primed animals.

The requirement of thymus competence for both humoral and cell-mediated steps in expulsion of Nippostorngylus brasiliensis from mice.

The worm damaging process (step 1 of Nippostrongylus brasiliensis expulsion from rodents) does not occur in congenitally thymus-deficient (nude) mice as determined by worm morphology, female worm fecundity, and kinetics of worm expulsion upon transfer into normal rats. Expulsion of damaged N. brasiliensis (step 2) does not occur subsequent to transfer of such worms from rats into nude mice. Morphological changes and reduced fecundity appeared in adult worms from normal thymus-bearing mice as early as the first day of patency (day 6 of infection). Thus, the worm damaging process is initiated several days earlier in mice than in rats and may, therefore, account for the reduced longevity of N. brasiliensis in mice compared with rats.

Bone marrow origin of mucosal mast cells.

Infection with the intestinal parasite Nippostrongylus brasiliensis stimulates an accumulation of mucosal mast cells (MMC) in the villi of the small intestine of normal but not athymic or W/Wv anemic mice. W/Wv mice are congenitally deficient in both MMC and skin and connective tissue mast cells (CTMC). Athymic mice have normal or elevated numbers of CTMC but are severely deficient in MMC. CTMC derive from the bone marrow. To determine the origin of MMC, athymic and W/Wv mice were given various hematopoietic or lymphoid tissues from normal littermate or beige mice and the MMC response to N. brasiliensis infection was evaluated. The MMC defect in athymic mice was repaired by grafts of thymus cells, thymus gland, or spleen cells, but not by bone marrow cells or anti-Thy 1-treated bone marrow or spleen cells. The MMC and CTMC defects of W/Wv mice were repaired by grafts of bone marrow, spleen cells, or anti-Thy 1-treated bone marrow or spleen cells. Neither the MMC nor the CTMC defect in W/Wv mice was repaired by grafts of thymus cells or thymus glands. These results indicate the following, MMC, like CTMC, derive from the bone marrow and not from the thymus. MMC require a thymic influence for development. Athymic mice possess bone marrow precursors for both MMC and CTMC but lack a thymus-dependent component necessary for MMC development. W/Wv mice lack both MMC and CTMC mast cell precursors but possess the thymus-dependent component required for MMC development.

Absorption of ablastic activity from mouse serum by using a Trypanosoma musculi population rich in dividing forms.

An in vivo assay of ablastin activity was developed by passive transfer of ablastic serum into nude mice. Preparations of Trypanosoma musculi that contained 35 to 50% dividing forms removed ablastic activity from mouse serum, but absorption of serum with a parasite preparation consisting of less than 5% dividing forms did not appreciably alter ablastic activity. These data suggest that ablastin is an antibody that can be absorbed onto homologous trypanosomes.

Rejection of the intestinal parasite Nippostrongylus brasiliensis by mast cell-deficient W/Wv anemic mice.

The ability of W/Wv anemic mice to accumulate mucosal mast cells and to reject the intestinal parasite Nippostrongylus brasiliensis was examined. W/Wv mice did not accumulate mucosal mast cells in response to infections with N. brasiliensis. They eliminated a primary infection more slowly than did their normal littermate controls but were as refractory as controls to second and third infections. W/Wv mice had higher serum titers of worm-specific immunoglobulin E than did controls. These results indicate that mucosal mast cells are not an absolute requirement for N. brasiliensis rejection.

Estradiol-induced wasting syndrome in conventionally reared and germ-free mice.

The pathogenesis of the estradiol-induced wasting syndrome is complex and cannot be explained solely by immunological impairment and subsequent infection.

Medium conditioned by spleen cells of Nematospiroides dubius-infected mice does not support development of cultured mast cells.

The ability of different conditioned media to support mast cell development from precursors in normal bone marrow was evaluated. Many mast cells developed in bone marrow cultures containing medium conditioned by concanavalin-A-stimulated spleen cells of normal mice, Trichinella spiralis-infected mice, or mice infected for 6 days by Nematospiroides dubius. By contrast, medium conditioned by concanavalin-A-stimulated spleen cells of mice having 18-day infections of the nematode N. dubius failed to support mast cell development. The difference between medium conditioned by spleen cells of mice having 6-day versus 18-day infections of N. dubius may be due to the life cycle stage of the parasite, larval or adult, present at those times. These results from cultures are consistent with those from in vivo studies in which mice given primary infections of N. dubius failed to develop the intestinal mastocytosis characteristic of nematode infections.

Immune response potential of mast cell-deficient W/Wv mice.

Immune responses of mast cell-deficient WBB6F1-W/Wv mice and their mast cell-sufficient littermates (LM: WBB6F1-W/+, Wv/+ and +/+) were compared. After a single intravenous injection of sheep erythrocytes (SE), polyvinylpyrrolidone or bacterial lipopolysaccharide, the antigen-specific IgM plaque-forming cell (PFC) response of W/Wv mice was similar to or greater than the response of LM mice. When both primary and secondary injections of SE or chicken gamma-globulin were given to mice and antigen-specific IgG PFC responses quantified, the response of W/Wv again was similar to or greater than that of LM mice. Serum titers of antigen-specific IgE were higher in W/Wv than in LM mice after injections of ovalbumin in alum or infections of Nippostrongylus brasiliensis. Ovalbumin-sensitized W/Wv and LM mice developed active systemic anaphylaxis after ovalbumin challenge. The ability of W/Wv mice to be sensitized for and elicit contact sensitivity (CS) reactions was studied using picryl chloride or dinitrofluorobenzene as sensitizing and challenge agents and quantifying 24-hour reactions by change in ear thickness. SE or methylated bovine serum albumin was used to sensitize and challenge mice for delayed-type hypersensitivity (DTH) reactions which were quantified at 24 h by change in foot pad or ear thickness. CS and DTH reactions of W/Wv and LM mice were similar. No evidence of immune deficiency of W/Wv mice was found.

Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W/Wv mice.

Mast cell-deficient W/Wv mice and their mast cell-sufficient littermates were given infections of Trichinella spiralis. W/Wv mice were slower than their littermates to expel adult T. spiralis. Repair of the mast cell deficiency of W/Wv mice by bone marrow grafting was accompanied by accelerated expulsion of T. spiralis.

Transferable drug resistance among Enterobacteriaceae isolated from human urinary tract infections.

Fifteen sulfonamide-resistant cultures isolated from urinary tract infections in eastern Nebraska were screened for transferable drug resistance by three methods. Seven of the 15 resistant cultures could transfer resistance of varying levels to two or more chemotherapeutic agents. Transfer of drug resistance occurred without accompanying transfer of chromosomal traits and required cell to cell contact. In mixed culture, the number of drug-resistant recipients increased exponentially, reaching a plateau 2 hr after mixing. Spontaneous or artificial elimination of resistance was found to be a rare event. In addition, several drug-sensitive isolates from urinary tract infections were shown to be competent recipients of drug resistance determinants. From these data, it appears that the transferable drug resistance observed was mediated by R factors.

Thymus dependence of tapeworm (Hymenolepis diminuta) elimination from mice.

Although normal mice eliminated the lumen-dwelling intestinal cestode Hymenolepis diminuta by day 21 post-cysticercoid inoculation, congenitally thymus-deficient (nude) mice maintained their work burdens. Nude mice grafted with thymus glands or injected with thymus cells eliminated their worms.