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D Mouton

Publications and source records attributed to D Mouton.

At least 37 records · Page 2Linked to original sources
PubMed1995

Specific and non-specific T-cell activation in high and low antibody-producing mice (selection IV-A).

The T-cell regulatory function has been evaluated in lines of mice genetically selected according to the High (H) and Low (L) antibody responsiveness to heterologous erythrocytes. The inhibition of antibody production following CD4+ subset depletion was stronger in L than in H mice. The dose of CD4-specific monoclonal antibody (MoAb) needed for a 50% inhibition of the anti-sheep erythrocyte antibody response was much lower in L mice, even when their responsiveness was improved by repeated antigen injections or by co-injection of lipopolysaccharide as an adjuvant. Lymph-node cells from L mice responded normally or even better than those from H mice to in vitro non-specific triggering via lectins, exogenous superantigens or CD3-specific MoAb. In contrast, the antigen-specific responses of the lymph-node cells from protein-primed mice were consistently lower in the Low responder mice. Altogether the results suggest that a defective stimulation of T helper lymphocytes by the antigen contributes to the weak antibody response of L mice.

Animals↗
PubMed1994

Comparison of 7,12-dimethylbenz(a)anthracene-DNA adduction in the epidermis of two lines of mice selected for resistance (CAR-R) or susceptibility (CAR-S) to skin carcinogenesis.

Two lines of mice were produced by bidirectional selective breeding: one resistant (CAR-R) and one susceptible (CAR-S) to two-stage skin carcinogenesis by dimethylbenz(a)anthracene and 12-O-tetradecanoyl-phorbol-13-acetate. The dimethylbenz(a)anthracene-DNA adduct formation was compared in the two lines by a postlabeling procedure so as to determine whether the striking interline difference observed as to tumor incidence could (in part) be due to differences in the formation of DNA-reactive metabolites. Results show that qualitatively, adduct profiles in CAR-R and CAR-S epidermis are similar. Quantitatively, the total binding level is slightly higher in CAR-S versus CAR-R mice during the 30-day follow-up. However, these minor differences do not increase in function of the response to selection observed through three consecutive generations. A 2- or 4-week promotion with 12-O-tetradecanoylphorbol-13-acetate enhances the decrease of adduct level in the two lines. This effect is somewhat more pronounced in CAR-S mice. Results strongly suggest that the expression of the genes responsible for CAR-R/CAR-S phenotypic difference affects mainly the postinitiation stages.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Genetics of chemical carcinogenesis--II. Papilloma induction and malignant conversion in susceptible (Car-s) and resistant (Car-R) lines of mice produced by bidirectional selective breeding and in their (Car-S X Car-R) F1 hybrids.

Susceptible (Car-S) and resistant (Car-R) lines of mice separated by 10 consecutive generations of bidirectional selective breeding present a very large difference in responsiveness to two-stage skin carcinogenesis. Car-S mice initiated with 0.5 micrograms 9,10-dimethyl-1,2-benzanthracene (DMBA) and promoted with 0.25 micrograms 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 77 days showed a papilloma incidence of 88% and a tumour multiplicity of 3.2 +/- 0.4 (mean +/- SE), with a tumour induction rate of 0.415. Car-R mice initiated with larger DMBA and TPA doses (50 micrograms and 20 micrograms respectively) and promoted for 111 days gave a comparable papilloma response: incidence 65%, tumour multiplicity 3.2 +/- 0.6 and tumour induction rate 0.288. The difference in papilloma response between the two lines is due to the interaction of genetic and environmental factors. In order to overcome the genetic effect with environmental factors and induce in Car-R a papilloma response comparable to that of Car-S, the DMBA dose had to be increased up to 100 times, that of TPA 40 times and the promotion time augmented by 44%. Papilloma to carcinoma conversion 112 days after the end of promotion depends on the DMBA and TPA doses applied. The number of carcinomas induced in Car-S mice and in (Car-S X Car-R) F1 hybrids was larger than that induced in Car-R mice, but the ratio of carcinoma conversion was lower, therefore a larger proportion of the small number of papillomas induced in the Car-R mice progressed to malignancy. The dominance effect measured in (Car-S X Car-R) F1 hybrids demonstrated that the susceptibility to papilloma induction was an incomplete dominant character (d/a = 0.38), whereas for carcinoma conversion the resistance was incompletely dominant (d/a = -0.49).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

T-cell compartment involvement in two high antibody responder lines of mice (HI and HII Biozzi mice) respectively susceptible and resistant to collagen-induced arthritis.

The T-cell compartment was investigated in two high antibody responder lines of mice respectively susceptible (HI) and resistant (HII) to chicken collagen (CII)-induced arthritis (CIA). Previous data had shown that both lines were high anti-CII Ab producers, without any TCR V-beta gene defect or membrane expression impairment. The present studies demonstrate that anti-CII proliferation is much lower in HII than in HI. These results are confirmed by the limiting dilution analysis of anti-CII T-precursor frequencies (1/991 in HI and 1/12175 in HII). The percentage of CD8+ T cells is constitutively higher in HII mice, this difference increasing after CII immunization. This finding suggests a suppressive effect accounting for resistance to CIA. However, no restoration of specific response was achieved by in-vivo or in-vitro depletion of CD8+ T cells. T clones specific for Chicken CII could be obtained only from primed HI mice. Four of five clones with CD8+ phenotype proliferated in vitro to native and denatured CII and showed cytotoxic function in an anti-CD3 redirected assay. The CD4+ clone was shown to proliferate on both HI and HII-pulsed APC, which rules out a major CII processing/presentation defect in HII.

Animals↗
PubMed1992

Processing and presentation of ovalbumin in mice genetically selected for antibody response.

Lines of mice selected for high or low antibody production to sheep red blood cells (H-I and L-I) were studied for their ability to process and present ovalbumin to a panel of 12 T-T hybridomas in two different H-2 haplotypes. When H-I and L-I spleen cells were used as antigen-presenting cells, no difference could be observed in the peptide generation by these mice compared to H-2-compatible B.10.Q and B.10.S spleen cells, respectively. Neither normal splenic L-I B-cells nor L-I thioglycolate-induced peritoneal macrophages were defective at presenting native ovalbumin, to six and eight different I-As-restricted T-T hybrids, respectively. Altogether, these results differ from previous findings which had indicated a deficiency in the processing and presentation of antigen by the low line, L-I.

Animals↗
PubMed1992

Genetics of nonspecific immunity: I. Bidirectional selective breeding of lines of mice endowed with maximal or minimal inflammatory responsiveness.

The genetic regulation of acute inflammatory reaction (AIR) was studied by the method of bidirectional selective breeding, used to produce a line of mice giving the maximal and a line of mice giving the minimal inflammatory reaction (AIR max and AIR min, respectively). The AIR was triggered by subcutaneous injection of a neutral substrate (suspension of polyacrylamide microbeads), and measured by the leukocyte and serum protein accumulation in the exudate. The two parameters are positively correlated and present a normal frequency distribution. The highly genetically heterogeneous foundation population was produced by the equipoised intercrossing of eight inbred strains of mice, and selective breeding carried out by assortative matings of extreme phenotypes. The response to selection in 11 consecutive generations was highly asymmetrical: a marked AIR increase in the AIR max and no change in the AIR min line occurred. The mean value of realized heritability in the AIR max line was 0.26 and 0.18 for cell and protein concentrations, respectively. The response to selection must have resulted from the interaction of seven to nine independent gene loci endowed with additive effects. The lack of response to selection of the AIR min line is discussed. The large inter-line difference opens new possibilities for studying the biochemistry and molecular genetics of inflammation, and also for investigating the beneficial or detrimental effect of inflammatory responses.

Acute Disease↗
PubMed1992

T-helper functions in lines of mice selected for high or low antibody production (Selection III): modulation by anti-CD4+ monoclonal antibody.

T-helper function was evaluated in mice genetically selected for high (H) or low (L) antibody (Ab) responsiveness to Salmonella flagellar antigen (Ag) (Selection III). In this Selection as opposed to what was demonstrated in Selections I, II and IVA, the interline difference was not proven to be based upon the modification of Ag processing and presentation at macrophage level. CD4+/CD8+ lymph node ratio is similar in HIII and LIII mice, both lines being equally susceptible to in vivo depletion of CD4+ T cells by GK 1-5 monoclonal antibody (mAb) treatment. Nevertheless, the Ab responsiveness of the two lines was differently modulated by GK 1-5 mAb: the inhibition of Ab responses to various Ag required lower mAb doses and was long lasting in LIII as compared to the transient effect of higher mAb doses observed in HIII. LIII mice were also refractory to Salmonella-induced reversion of GK 1-5 mAb inhibition. Moreover, in vitro specific I proliferation was constantly lower in LIII, though its IL-2 production was unexpectedly similar to that of HIII T cells. Results of in vivo and in vitro experiments are thus consistent with a defective response of T-helper cells to immunogenic challenge in LIII mice.

Animals↗
PubMed1992

EASEing in the 90s.

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Hospitals, County↗
PubMed1991

Variations in susceptibility to Leishmania amazonensis infection in lines of mice selected for high or low immunoresponsiveness.

The degree of resistance to a local Leishmania amazonensis challenge has been compared in lines of mice obtained by selective breeding for high or low immunoresponsiveness: High and Low antibody responder mice of Selections I and II (HI, HII and LI, LII lines) and high and low responder mice to T mitogen PHA (Hi/PHA and Lo/PHA). The aim of this preliminary study was to focus attention on genetic differences related with well defined immune characteristics. Clear-cut results were obtained, both HI and HII mice developed large and disseminating lesions, the rate of symptom aggravation being faster in HII, while LI and LII proved resistant to parasites, only small and transient lesions being observed for them during a 150 days follow up. The outcome of infection also differs in Hi/PHA and Lo/PHA mice, Hi/PHA having a resistant and Lo/PHA a susceptible phenotype.

Animals↗
PubMed1991

Isotypic distribution of antibody responses in lines of mice selected for high or low immunoresponsiveness.

1. The isotype distribution of antibody (Ab) responses to Salmonella antigens (Ag) was investigated in high (H) and low (L) Ab responder lines of mice from Selections III and IV carried out for responsiveness to flagellar (f) and somatic (s) Ag, respectively. 2. Primary immunization resulted in higher Ab titers of all isotypes in response to both Ag in H mice from both selections and was confirmed after booster injections. The interline difference (H-L) in response to the distinct isotypes ranged from 3.0 to 7.0 log2 to Ag f in Selection III and from 2.0 to 5.1 log2 to Ag s in Selection IV. 3. Comparison of isotype production to 3 Ag in Selections I, II, III and IV demonstrated that: 1) the highest responses in all mice are those against the selection Ag, 2) the isotypic pattern depends on both the Ag injected and the host's genetic constitution, and 3) the presence or lack of a multispecific effect is not due to isotype-restricted regulation.

Animals↗
PubMed1990

Spontaneous rheumatoid-like arthritis in a line of mice sensitive to collagen-induced arthritis.

Twenty-eight percent of 13-month-old male mice of the high antibody responder line of Biozzi's selection I (HI) spontaneously developed a long-lasting inflammatory arthritis. This disease was clinically and histologically similar to human rheumatoid arthritis. The synovium of joints and some tendons was hypertrophied, with thickening of the synovial cell layer and infiltration by polymorphonuclear and mononuclear leukocytes. In some cases, synovial pannus formation led to destructive damage of articular cartilage and bone. Rheumatoid factor and antinuclear, anti-DNA, and anti-type II collagen (CII) antibodies were often found in the sera of both arthritic mice and clinically normal littermates. The presence of CII autoantibodies in this line of mice suggests that a potentially harmful anti-CII T cell autoimmunity can also develop spontaneously and lead to joint damage. Moreover, HI mice are also susceptible to collagen-induced arthritis, while a closely related mouse line (HII) is resistant to both diseases. These data support the hypothesis that collagen-induced arthritis is pathogenetically related both to this spontaneous arthritis and to rheumatoid arthritis.

Animals↗
PubMed1990

Polymorphism of Tcrb and Tcrg genes in Biozzi mice: segregation analysis of a new Tcrg haplotype with antibody responsiveness.

Tcrb and Tcrg gene polymorphism was investigated in high (H) and low (L) responder Biozzi mice from selection I, II, and GS by Southern blot analysis with appropriate V and C probes. No polymorphism of the Tcrb haplotype was detected between H and L mice in all selections which were all found to be of the BALB/c type. The H-I and H-II g genotype was of BALB/c and DBA/2 type, respectively. In contrast, a new Tcrg haplotype shared by L-I and L-II mice was identified and characterized by C gamma 1, 2, 3, C gamma 4, V gamma 1, 2, 3, V gamma 5, and V gamma 6 restriction fragment length polymorphisms (RFLPs). Tcrg genotypes were not fixed in the GS selection and two additional new haplotypes were identified in two L-GS mice. An attempt was made to correlate the L-I g genotype with the low responder status by analyzing g haplotypes among highest and lowest responder (H-I X L-I)F2 hybrids immunized with sheep red blood cells (SRBC). No correlation was found in this segregation study, whereas a highly significant one was established with the H-2 haplotype, a locus already known to participate in the genetic control of H-I/L-I difference. The lack of correlation between SRBC response and the Tcrg genotype was consistent with the heterogenous g haplotypes found in mice of the GS selection. Together, the present results suggest that H and L mice have the same Tcrab potential repertoire and that T-cell receptor (Tcr) genes cannot be considered as immune response genes in this model. Our results also indicate that the F2 segregation analysis, given a polymorphic gene, is suitable for an investigation of its immune response functions.

Animals↗
PubMed1990

Genetics of chemical carcinogenesis. 1. Bidirectional selective breeding of susceptible and resistant lines of mice to two-stage skin carcinogenesis.

Six generations of a bidirectional selective breeding model for producing lines of mice susceptible (Car-S) and resistant (Car-R) to two-stage skin carcinogenesis are described. Initiation was with 9,10-dimethyl-1,2-benzanthracene (DMBA single application), and promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA twice weekly). The selective breeding was initiated with a highly genetically polymorph foundation population, produced by the intercrossing of eight inbred mouse strains. The Car-S line was produced by assortative mating of the mice presenting the largest number of tumors induced by low DMBA and TPA doses, the Car-R line by mating tumorless mice or mice showing the smallest number of tumors induced by large DMBA and TPA doses. The character investigated was expressed as per cent tumor incidence and as tumor multiplicity per mouse. The mean heritability of the susceptibility character for the two first generations was 0.84 for tumor incidence and 1.3 for tumor multiplicity; these values decreased to 0.53 and 0.44 respectively for the two consecutive generations. The heritability of the resistance character maintained a constant value of 0.29 +/- 0.04 for tumor incidence, and 0.53 +/- 0.08 for tumor multiplicity. The progressive response to selection indicates that the characters investigated are subject to polygenic regulation, even though some genes may have a major effect on the susceptibility character. The interline separation in F5, challenged with the same initiation and promotion schedule, is very large. In the Car-S line, tumor incidence was 82.5% and tumor multiplicity 4.9/mouse on promotion day 49, whereas the corresponding values for the Car-R line were 4.5% and 0.1/mouse on promotion day 81.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Genetics of acute inflammation: inflammatory reactions in inbred lines of mice and in their interline crosses.

Acute inflammation is induced by the subcutaneous injection of swollen polyacrylamide microbeads, its intensity measured by the cell and protein concentration of the local exudates. A large and continuous range of responses is obtained in different inbred strains of mice, which suggests a polygenic control of the inflammatory response. The variable levels of the global dominance observed in F1 hybrids issued from several parental combinations indicated that the pattern of alleles controlling high or low response was different in each parental strain. Balanced intercrossing of the 8 inbred strains studied has provided a genetically heterogeneous F3 population, presenting a high variability of responses. The value of the genetic part of F3 phenotypic variance, the spread of the interstrain differences, as well as the polygenic nature of the regulation of inflammatory responses pointed out the possibility to perform a bidirectional genetic selection by using the F3 mice as the foundation population, and response to microbeads as the selective phenotypic character.

Acrylic Resins↗
PubMed1989

Collagen-induced arthritis in Biozzi mice. Joint involvement is not correlated with collagen II IgG2a autoantibodies nor restricted to only H-2q and H-2r.

High (H) and low (L) immune responder "Biozzi" mice, obtained by four different selections, were investigated for their ability to develop collagen-induced arthritis. Both LI and LII lines--characterized by their low antibody responses to a wide variety of Ag--developed arthritis though they do not bear the susceptible H-2q and H-2r haplotypes. Out of the two lines (HI and HII) selected for their high antibody responses and bearing H-2q, only one (HI) developed arthritis. Both the lines with amplified high or low antibody responses (HG and LG), and the lines differing in the levels of cell-mediated immunity (Hpha and Lpha), failed to develop arthritis. Collagen II autoantibodies were found in all the lines: the responses being high (HI and HG), low (LI, LII and LG), or intermediate (HII, Hpha and Lpha). The level of IgG2a autoantibodies, presumed to be the most pathogenic, was low in two (HI and LII) of the three arthritic lines, and was high in the unaffected HG line. These results show that this arthritis is not solely restricted to H-2q and H-2r haplotypes, and argue against a correlation between collagen autoantibody levels and disease incidence.

Animals↗
PubMed1989

Inheritance of immune responsiveness, life span, and disease incidence in interline crosses of mice selected for high or low multispecific antibody production.

High (H) and low (L) antibody responder lines of mice separated by selective breeding present a maximal interline difference in antibody (Ab) response to Ag of different specificities (general genetic regulation). The analysis of SRBC agglutinin response in H line, L line, F1 hybrids, F2, and backcross segregants demonstrates that Ab responsiveness is a polygenic trait regulated by the additive interaction of 5 to 7 independent loci, with an incomplete dominance (44% +/- 7%) of the high response character, and a 30% +/- 10% impact of the environmental factors. The life span of H, L, F1, F2, and backcross populations is correlated positively with 2-ME-resistant agglutinin response (r = 0.97, p less than 0.001) and negatively with 2-ME-sensitive agglutinin response (r = 0.95, p = 0.01) (interpopulation correlation). Similar correlations are also observed in individuals of the various populations, especially in F1 x L backcross, in which the largest phenotypic variance is found. The positive correlation between Ab responsiveness and life span was confirmed by ELISA titration for distinct IgG isotypes (intrapopulation correlation). Malignant lymphomas and chronic nephritis were the two most common diseases observed. The age-adjusted incidence of such diseases, which is largely affected by environmental factors, accounts for the longer life span of H, as compared with L, mouse populations. The longevity of the 30% or less survivors, chiefly determined by the rate of physiologic aging, is a polygenic character regulated by the cumulative interaction of 3 to 7 independent loci, with a complete dominance of the long life trait and an impact of the environmental factors of about 60%. Thus we have grounds for regarding general Ab responsiveness and life span as polygenic traits regulated by a small number of identical or closely linked gene loci, and immune responsiveness as a defense mechanism against neoplastic and inflammatory diseases.

Aging↗
PubMed1989

Evaluation of T helper function in lines of mice selected for high or low antibody production: quantitative inhibition of immune responses by anti-L3T4+ monoclonal antibody.

The potentialities of T helper cell compartment were compared in lines of mice selected for high or low Ab production against heterologous erythrocytes (H1 and L1 mice) by investigating the "in vivo" and "in vitro" modulation of immune responses by GK 1-5 anti-L3T4+ mAb. FACS analysis showed a frequency of L3T4+ cells similar in non-immunized mice of both lines. However, LI mice were more susceptible to inhibition of the IgG Ab response to SE when injected GK 1-5 prior to immunization. The "in vitro" proliferation of T cells specific for HEL was higher in HI than in LI LN cultures, and a higher GK 1-5 mAb concentration had to be applied to HI cultures in order to produce the inhibitory effect. In contrast, during MLR, the capacity for T proliferation was similar in HI and LI cultures stimulated by a common F1 target. This allo-Ag-induced proliferation was inhibited at similar GK 1-5 mAb concentrations in the two lines. These results demonstrate that there is no intrinsic L3T4+ cell deficiency in LI mice. Differences in GK 1-5 mAb required for inhibition of responses to Ag (other than allo-Ag) in HI and LI mice are mainly due to different macrophage T cell triggering.

Animals↗