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At least 19 recordsLinked to original sources
PubMed1977

Immunologic tolerance to HGG in mice. I. Suppression of the HGG response in normal mice with spleen cells or a spleen cell lysate from tolerant mice.

Adoptive transfer of spleen cells or spleen cell lysates from mice tolerant to human-gamma-globulin (HGG) specifically suppressed the response of normal syngeneic recipients to HGG. The suppressive activity could be transferred for over 100 days after tolerance induction. The suppression induced by both spleen cells and spleen cell lysate was found to be specific as evidenced by a normal response to a challenge with turkey-gamma-globulin or goat erythrocytes. The activity of the suppressive lysate could be removed by passing the material through an HGG immunoadsorbent column but not by passing it through an anti-HGG column or a BSA column. These results indicated that the factor had antigen specificity and was probably not antigen-antibody complexes. That this suppression was not due to a shifting of the kinetics of the antibody response has also been demonstrated. The antigen-specific suppressor factor in the tolerant spleen cell lysates was a protein with a m.w. of approximately 45,000 daltons. The kinetics of the appearance of both suppressor cells and suppressor factor were consistent with a mechanism of active suppression functioning in the maintenance of tolerance to HGG.

Animals↗
PubMed1979

Chemical carcinogenesis in nude mice: comparison between nude mice from homozygous matings and heterozygous matings and effect of age and carcinogen dose.

The incidence and latency periods for local tumor development after sc injection of 3-methylcholanthrene (MCA) into 30-day-old nude mice (nu/nu partially inbred on the CBA/H background) derived from homozygous matings (nu/nu times nu/nu) or heterozygous matings (nu/+ times nu/+) were comparable and did not differ with the immunologically normal controls, even when the carcinogen dosages ranged from 0.01 to 0.10 mg. Similarly, no differences in tumor incidence or latency periods between nude mice from homozygous or heterozygous matings as well as their immunologically normal controls were observed when weight-adjusted doses of MCA equivalent to 0.02 to 0.10 mg in the 30-day-old mice were administered at 120, 210, or 360 days of age. Tumor incidence was lower in nude mice and normal mice when MCA was administered at 210 and 360 days of age, especially in mice given the lower dose of MCA. The lower dosages of MCA (0.01-0.05 mg) had no detectable immunodepressive effects in normal mice. Thus the "normal" tumor incidence in nude mice after MCA administration could not be attributed to: 1) the effect of humoral thymus gland function (in the nude mice derived from heterozygous matings), 2) the immunodepressive effects of the carcinogen (the lower MCA dosages are not immunodepressive), or 3) the age of the mice at administration. These results argue against the thymus dependency of immunologic surveillance.

Age Factors↗
PubMed1978

Giardiasis in mice. I. Prolonged infections in certain mouse strains and hypothymic (nude) mice.

The natural history of Giardia muris has been studied in inbred mouse strains and hypothymic (nude) mice derived from a specific pathogen-free facility. Although giardiasis was readily established in several mouse strains, marked variation was observed in the time course of spontaneous elimination of the parasite. During a 10-week study, fecal excretion of Giardia cysts remained relatively constant in C3H/He mice, but decreased at a variable rate in other mouse strains. Resistance to reinfection was greater in strains in which the duration of primary infection was relatively short. Hypothymic (nude) mice derived from a strain showing a relatively rapid elimination of Giardia (BALB/c) maintained a stable infection with high cyst counts. Nude mice reconstituted with lymphoid cells from syngeneic thymus-intact mice showed a progressive reduction in cyst excretion and reconstitution with limited numbers of lymphoid cells from thymus-intact mice previously exposed to Giardia accelerated resolution of infection. In nude mice, giardiasis was associated with a reduction in the villus-crypt ratio of jejunal mucosa, but the degree of change was greater in nude mice reconstituted with lymphoid cells. This Giardia model involving inbred strains and nude mice permits further dissection of the function of thymus-derived cells in intestinal immune responses and induction of changes in small bowel morphology.

Animals↗
PubMed1976

Mammary tumorigenesis in chemical carcinogen-treated mice. VI. Tumor-producing capabilities of mammary dysplasias in BALB/cCrgl mice.

Two types of mammary dysplasias occurring in 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/cCrgl mice were transplanted into the cleared mammary fat pads of syngeneic mice for an assessment of their growth behavior and tumor potentials. Keratinized nodules, numerous in DMBA-treated, pituitary isograft-bearing BALB/cCrgl mice, produced primarily ductal outgrowth in control mice and very few tumors (7%) 56 weeks after transplantation. Such dysplasias transplanted into mice bearing pituitary isografts exhibited lobuloalveolar development and produced a higher incidence of tumors (32%). Hyperplastic alveolar nodules (HAN), though relatively rare in DMBA-treated BALB/cCrgl mice, produced lobuloalveolar outgrowth in control mice and had a 100% tumor incidence. Four HAN outgrowth lines were developed by serial transplantation of samples of the nodule outgrowths. The tumor potentials of these nodule lines in intact controls and ovariectomized mice was determined over several transplant generations. The tumor potentials of two of the three nodule lines were decreased in the absence of ovarian hormones. However, the growth of 23 mammary tumors derived from these nodule lines and of nine derived from in situ primary tumors was unaffected by the absence of the ovary. These results, along with those published previously, suggest that mammary tumors in chemical carcinogen-treated mice arise from several precursor populations. These preneoplastic populations comprise both alveolar and ductal hyperplasias.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Enhancement of heterotransplanted human tumor graft survival in nude mice treated with antilymphocyte serum and in congenitally athymic-asplenic (Lasat) mice.

The latency period, success rate, and minimal cell inoculum size required for transplantation of continuously passaged human tumor lines into congenitally athymic (nude) mice, antilymphocyte serum (ALS)-treated congenitally athymic (nude) mice, and congenitally athymic-asplenic (lasat) mice were compared. The 11 tumor lines studied included examples of breast adenocarcinoma, transitional cell carcinoma, osteosarcoma, fibrosarcoma, Hodgkin's disease, malignant melanoma, and rhabdomyosarcoma. Of these 11 tumor lines, 3 were successfully transplanted into nude mice, compared to 5 of 10 tumor lines in ALS-treated nude mice and 9 of 11 lines in lasat mice. Moreover, the latency period was shorter and the minimal cell inoculum size was lower for lasat mice than for either nude or ALS-treated nude mice. Despite this enhancement of heterotransplantation into lasat mice and despite the growth of large local masses, no evidence of distant metastases was found.

Animals↗
PubMed1975

Spontaneous arteritis and glomerulitis in mice. A comparison of light and electron microscopic renal changes in PN/n, NZB/BL, 101/MAC, and CBA/MAC mice.

Four PN/n mice between 12 and 17 months of age had fibrinoid necrosis of the renal arteries, but 32 mice up to the age of 17 months showed no consistent change in the media or intima of the renal arteries although perivascular cuffing with round cells was prominent from 9 months of age. Glomerulitis, indicated by increase in the mesangium on light microscopy, affected most mice over 7 months of age, and dense deposits on electron microscopy were present in most mice from 7 months of age. These changes occurred significantly more frequently than in CBA/MAC mice; the 101/MAC showed an intermediate frequency, and the pattern in a small sample of NZB/BL mice resembled that of the PN/n mice. Basement membrane thickening increased with age from 3 weeks in all of the strains but more often included dense deposits in PN/n mice. Splitting of the glomerular basement membrane in very young mice in all strains was not considered relevant and may have been developmental. Failure consistently to detect glomerulitis earlier by electron microscopy than by light microscopy was attributed to the greater sampling error of the former. Unidentified dense bodies in glomerular epithelial cells occurred at all ages in all strains, so the suggestion that they were virus particles relevant to the disease was not sustained. Intraobserver variation studies showed satisfactory repeatability for light microscopy and for dense deposits and basement membrane thickening, but the dense bodies were not detected with acceptable reproducibility, a difficulty partly due to technical variation.

Age Factors↗
PubMed1977

Studies on antigen-induced arthritis in mice. II. Immunologic correlates of arthritis susceptibility in mice.

Antigen-induced arthritis was developed in mice as a model of human rheumatoid arthritis by using methylated bovine serum albumin (mBSA) as antigen. It was found that most strains were susceptible, whereas CBA mice were resistant. We therefore investigated the humoral and cell-mediated immune responses to mBSA in resistant mice (CBA) and susceptible mice (exemplified by C57BL) to determine whether these were associated with susceptibility to arthritis. The resistant strain (CBA) differed from the suceptible strains in the following respects. First, there was a lower humoral immune response to mBSA as measured by passive hemagglutination, but this could be overcome by a larger immunogenic dose. Secondly, there were differences in response to low doses of DNP-mBSA after mBSA carrier preimmunization. Thirdly, there were striking differences in delayed-type hypersensitivity (DTH) to mBSA as determined by a radioisotopic assay in vivo; the response of CBA mice occurred early, at 5 days, declined quickly, and was weaker, whereas that of C57BL mice developed later and was long sustained. Genetic studies of the DTH response with hybrids and backcrosses showed an oligogenic control of immune responsiveness, with one gene being linked to the H-2b allele of the susceptible C57BL mice, and another being independent of the H-2 complex. Our findings indicate that in mice, susceptibility to antigen-induced arthritis with mBSA correlates with a higher responder state to this antigen, and that T cells are the major if not the only determinant of the high responder state.

Animals↗
PubMed1979

Serum immunoglobulin levels in mice. Determination of the low IgA level in AKR mice by an irradiation-resistant factor.

A comparison was made between the serum immunoglobulin (Ig) levels in H-2 compatible AKR and C3H mice. The IgG1 and especially the IgA level in preleukemic AKR mice was much lower than in age-matched C3H mice, while the IgM concentration was hardly different for AKR and C3H. Lethally irradiated AKR and C3H mice reconstituted with syngeneic bone marrow (BM) cells showed a return to serum Ig levels which are normal for these strains. In AKR mice reconstituted with C3H BM cells low IgA levels were observed. On the other hand, in C3H mice reconstituted with AKR BM cells high quantities of IgA appeared, showing the AKR allotype. It is concluded that the low serum IgA concentration in AKR mice is not a reflection of a genetically determined inability of the B cell line to produce IgA, but rather a manifestation of a genetically determined capability to prevent IgA synthesis.

Animals↗
PubMed1979

Further characterization of immunological unresponsiveness induced in mice by ultraviolet radiation. Growth and induction of nonultraviolet-induced tumors in ultraviolet-irradiated mice.

Ultraviolet (UV)-irradiated mice were compared with unirradiated mice for their susceptibility to primary and transplanted tumors etiologically unrelated to UV radiation. Although UV-irradiated mice are unable to reject transplants of highly antigenic syngeneic tumors induced by UV light, the growth of syngeneic, non-UV-induced tumors generally was not accelerated in these animals. Furthermore, UV-irradiated mice were no more susceptible to the induction of primary leukemias, mammary tumors, or sarcomas than were unirradiated animals. Tests of immune responses to weak transplantation antigens showed that UV-irradiated mice rejected H-Y-incompatible skin grafts as vigorously as did normal animals, and that the primary in vitro cytotoxic responses of spleen cells from UV-irradiated mice to trinitrophenyl (TNP)-modified syngeneic cells and to Hh antigens were unaffected. We conclude that the susceptibility of UV-irradiated mice to challenge with UV-induced tumors represents a selective unresponsiveness, and that it is not attributable to a generalized deficiency in the immune response to tumor-specific antigens or to weak transplantation antigens.

Animals↗
PubMed1977

Studies on immune responses to larval cestodes in mice. Increased susceptibility of certain mouse strains and hypothymic mice to Taenia taeniaeformis and analysis of passive transfer of resistance with serum.

Various inbred strains of mice vary markedly in their susceptibility to the larvae of the cestode, Taenia taeniaeformis. Males are generally more susceptible than females and the most susceptible common inbred mouse strains are those which are deficient in C5 and/or C4 components of complement. However, no genetic evidence is yet available to implicate loci controlling complement levels in susceptibility/resistance, and multiple genetic factors appear to be operative. Hypothymic, nu/nu ("nude") mice of the relatively resistant mouse strain, BALB/c, are highly susceptible in that cystic larvae in the liver develop in large numbers and more rapidly than in intact BALB/c.nu/+litter-mates. Cyclophosphamide pretreatment also increases the susceptibility of relatively resistant strains of mice in terms of both the number and size of liver cysts. Hypothymic and intact mice can be protected, absolutely, by an injection of serum from infected intact mice, provided the serum is given to recipient mice close to the time of oral egg administration. The protective activity of immune serum is absorbed totally by staphylococcal protein A-Sepharose columns and can be abolished by treatment of recipients with cobra venom factor. Cyst fluid from established larvae facilitates the activity of subhaemolytic amounts of guinea pig complement in a standard direct PFC assay. The data suggest that complement-fixing antibodies are responsible for inhibition of establishing larvae in mice and that one method of protection for established cystic larvae involves the alteration of host complement activity within the cyst.

Age Factors↗
PubMed1978

Resistance and susceptibility of mice to bacterial infection: course of listeriosis in resistant or susceptible mice.

Resistance and susceptibility to Listeria monocytogenes in mice was found to be related to (i) the innate ability of the nonimmune macrophages to kill or inhibit the growth of the organism during the first 24 to 48 h after infection, and (ii) the time of onset of acquired cell-mediated resistance. Resistant C57Bl/6 mice were 10 times more efficient than susceptible BALB/c mice at suppressing the early growth of Listeria in the liver. Furthermore, the onset of acquired immunity occurred 24 to 48 h earlier in C57Bl/6 than in BALB/c mice. Acquired immunity was measured by (i) fall in bacterial numbers in spleen and livers of infected mice (ii) adoptive transfer of immunity to normal mice by using spleen cells from infected mice, (iii) delayed-type hypersensitivity skin testing, and (iv) uptake of tritiated thymidine by lymphocytes in the spleen.

Animals↗
PubMed1976

Uptake of circulating iron by the duodenum of normal mice and mice with altered iron stores, including sex-linked anemia: high resolution radioautographic study.

Using electron microscopy radioautography, the deposition of intravenously administered iron in the duodenal epithelium was studied in normal mice, iron-overloaded and iron-deficient mice, and in mice with X-linked anemia (gene symbol sla) 4 and 24 hours after injection of 59Fe. The resolution of radioautography with 59Fe was determined with a line source and the distance from the hot line within which half of the grains fell (HD value) was 1650 A. In normal, iron-overloaded, and sla mice, radioiron was localized in the undifferentiated crypt cells at 4 hours and in the absorptive cells of the luminal half of the villi, at 24 hours. At both times, the vast majority of the grains was seen over the areas rich in free ribosomes and rough endoplasmic reticulum. In iron-deficient mice, grains were not found at either time. The amount of iron incorporated in the crypt cells was related to the size of the body iron stores. It is postulated that the amount of iron incorporated in the crypt cells is the result of interaction between uptake and return to the blood of the circulating iron. Once the crypt cells have differentiated into absorptive cells, the uptake and recirculation of iron from and to the blood would cease, leaving an amount of "message" iron which determines the absorptive cell's subsequent capacity for iron transfer to the plasma. In sla mice, in spite of tissue iron deficiency, the amount of iron deposited was similar to that of normal mice and markedly increased after treatment of the anemia. The accumulation of iron in the crypt cells may result from the decreased return to the blood of the incorporated circulating iron, due to the postulated deficient iron carrier mechanism in sla, or may be a consequence of increased avidity of the absorptive cells for circulating iron. In either event, the result would be that the absorptive cell receives an inappropriate message with resulting inappropriate absorption of iron.

Anemia, Hypochromic↗
PubMed1979

Genetics of xenotropic virus expression in mice. I. Evidence for a single locus regulating spontaneous production of infectious virus in crosses involving NZB/B1NJ and 129/J strains of mice.

The extent of infectious xenotropic virus expression in homogenized splenic tissues from the high-virus-expressing NZB/BINJ mice and the non-virus-expressing 129/J mice and their crosses has been examined. The data suggest that a single autosomal "dominant-like" gene controls the spontaneous production and release of infectious xenotropic virus in NZB mice. Analysis of infectious virus production in second-backcross families [(F1 X 129) X 129] confirmed this conclusion. Variations in the amount of X-tropic virus released were evident in all genetic crosses. Virus titers (expressed as focus-forming units per milliliter) of supernatant fluid ranged from high levels in the NZB mice to somewhat lower levels in crosses involving the 129 mice. In the absence of a definite pattern in the titers observed in the genetic crosses studied, the term dominant-like is proposed for the single gene regulating the expression of X-tropic virus in NZB mice.

Animals↗
PubMed1976

Immunity to Plasmodium Berghei yoelii in mice. I. The course of infection in T cell and B cell deficient mice.

The course of infection with 17X nonlethal Plasmodium berghei yoelii was examined in BALB/c mice which were deficient in either T cells or B cells. Markedly increased parasitemia and mortality were observed in athymic (nude) mice which had been backcrossed on a BALB/c background (T cell deficient) compared to similar mice which had been grafted with neonatal BALB/c thymus, and were also observed in BALB/c mice suppressed from birth with goat antiserum to mouse mu-chain (B cell deficient) compared to age- and sex-matched BALB/c controls. These results establish the requirement for the presence of both T cells and B cells for effective resistance to an intercurrent infection with 17XNL P.b. yoelii in adult BALB/c mice. Mechanisms by which the requirement for both T cells and B cells could be explained were discussed. The model of mu suppression was shown to be a valuable tool for an evaluation of the cellular basis of immunity to an infectious disease.

Animals↗
PubMed1979

Studies of congenitally immunologic mutant New Zealand mice. II. Absence of T cell progenitor populations and B cell defects of congenitally athymic (nude) New Zealand Black (NZB) mice.

Congenitally athymic (nude) mice on an NZB, NZW, and BALB/c background were produced by repetitive selective backcrossing. F'12 generation nude mice of these three strains were compared to their littermate nu/+ controls with respect to survival, histology, blood counts, splenic surface markers, response to mitogens, spontaneous plaque-forming cells, and appearance of naturally occurring thymocytotoxic antibodies (NTA). Under specific pathogen-free conditions, NZB nude mice survive less than 3 weeks, dying of a runting-like disease with infection by local normally noninvasive organisms. A contributing factor to his premature death is the relative absence of T cell progenitor populations in the NZB nude vs NZW nude or BALB/c nude groups. Furthermore, NZB nude mice have a significantly earlier appearance of NTA than nu/+ littermates and likewise appear to have heightened spontaneous polyclonal B cell responses against the haptens dansyl, nitroiodophenyl, trinitrophenyl,2,4 dinitrophenyl, and sulfonate. It is suggested that NZB mice have several critical immunologic defects, including abnormalities of thymic epithelial cells, T cell differentiation pathways, and chronically polyclonal activated B cell populations. These defects interact to produce the clinical expression of autoimmunity.

Animals↗
PubMed1977

Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system.

Tolerance can be induced in adult mice by a single intravenous injection of 0.5 mg dinitrophenylated bovine gamma globulin. The cellular mechanism of the unresponsive state is different depending upon whether the tolerance is induced in normal intact adult mice or in reconstituted, irradiated mice. The tolerant state induced in intact mice is characterized by a high avidity of the residual antibody-forming cells in partially tolerant animals and a prompt reversibility on cell transfer. The overall properties of this unresponsive state are consistent with the hypothesis that it is mediated by the production of small amounts of high affinity antibody in response to the tolerance-inducing injection of antigen. In contrast, the unresponsiveness induced in reconstituted, irradiated mice by the same procedure was characterized by a low avidity of the residual antibody-forming cells in partially tolerant animals and stability on transfer of spleen cells from unresponsive into irradiated recipients. No suppressor cell activity was detected and mixed cell transfer studies were consitent with the view that this unresponsive state represented a B-lymphocyte clonal deletion. The presence or absence of T lymphocytes in the population of cells used for reconstituting the irradiated recipients did not effect the ease of tolernace induction or the cellular mechanism of the tolerant state which was produced. If irradiated mice reconstituted with B and T lymphocytes were rested for 2 wk before tolerance induction then a reversible "high affinity"-type tolerance is obtained such as is typical of normal intact animals. Restorationof a "normal" response to the tolerance-inducing injection of antigen is dependent upon the presence of thymus cells in the population of cells used for reconstitution. It is suggested that the structural integrity of the lymphoid tissue is critical in determining whether B cell will be rendered tolerant after exposure to antigen in vivo.

Age Factors↗
PubMed1977

Immunity to sporozoite-induced malaria infeciton in mice. I. The effect of immunization of T and B cell-deficient mice.

The cellular basis of immunity to sporozoites was investigated by examing the effect of immunization of T and B cell-deficient C57BL/6N X BALB/c AnN F1 (BLCF1) mice compared to immunocompetent controls. Immunization of T cell-deficient (ATX-BM-ATS) BLCF1 mice with x-irradiated sporozoites did not result in the generation of protective immunity. The same immunization protocols protected all immunocompetent controls. In contrast, B cell-deficient (micron-suppressed) BLCF1 mice were protected by immunization in the majority of cases. The absence of detectable serum circumsporozoite precipitins or sporozoite neutralizing activity in the micron-suppressed mice that resisted a sporozoite challenge suggests a minor role for these humoral factors in protection. These data demonstrate a preeminent role for T cells in the induction of protective immunity in BLCF 1 mice against a P. berghei sporozoite infection.

Animals↗