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Biomedical subjects

P H Lagrange

Publications and source records attributed to P H Lagrange.

At least 109 records · Page 6Linked to original sources
PubMed1983

Paracoccidioidomycosis in silica-treated rats.

An attempt is made to evaluate the importance of macrophages in the early local reaction to infection caused by the fungus Paracoccidioides brasiliensis. With this purpose, an attempt was made to impair macrophagic activity in the site of the fungal inoculum, by means of previous injections of silica. Twenty male rats were intraperitoneally infected with yeast cells of the fungus. Ten of the rats were injected intraperitoneally with silica particles twice, namely 24 and 4 h before the infection. All the animals were killed 4 wk after fungal inoculum. The results showed that the disease was aggravated in rats pre-treated with silica, clearly demonstrated by the 100% metastatic pulmonary involvement, in contrast with only 40% observed in the non-treated controls.

Animals↗
PubMed1983

Deficit of interleukin 2 production associated with impaired T-cell proliferative responses in Mycobacterium lepraemurium infection.

C57BL/6 and BALB/c mice were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). At various times after infection, spleen cells were tested for their capacity to proliferate in vitro in response to concanavalin A (ConA) and to allogeneic cells. The generation of alloreactive cytotoxic T lymphocytes was also studied. The mitogen- and allogeneic-cell-induced blastogenesis of splenocytes from MLM-infected C57BL/6 and BALB/c mice was shown to be depressed during infection. The maximal decrease occurred 6 months after infection. Conversely, no reduction in the ability to generate alloreactive cytotoxic T lymphocytes was observed even after 6 months of infection. At the same time, interleukin 2 (IL2) activity generated by ConA stimulation of infected splenocytes was measured in both strains. IL2 activity in the ConA-stimulated culture supernatants was decreased as early as 1 month after MLM inoculation as compared with supernatants from age-matched control mice. Thus, IL2 production by infected-mouse spleen cells was shown to decline earlier than their proliferative responses to ConA and to allogeneic cells. ConA-induced T-cell blasts from infected mice showed a reduced ability to proliferate when incubated with an IL2-containing reference supernatant from ConA-stimulated normal spleen cells. These data suggest that a defect in IL2 production and utilization might contribute to the impairment of T cell-mediated immunity observed in MLM-infected mice.

Animals↗
PubMed1983

[Effect of moderate protein-calorie deprivation on cell-mediated immunity in mice].

Mild protein-calorie deprivation in mice decreases their early nonspecific inflammatory response to an injection of BCG or tuberculin into the footpad. After an injection of BCG, the size of the granuloma and the delayed hypersensitivity reaction to tuberculin significantly decreased. This decrease in cell-mediated immunity was paradoxically accompanied by a fall in bacillus multiplication at the popliteal ganglion, i.e. the site of BCG injection. A reduction in microbial multiplication was also observed in the spleen after intraperitoneal injection of Listeria and in the liver after intravenous injection.

Aging↗
PubMed1983

Surface Lyt phenotype of suppressor cells in C57BL/6 mice infected with Mycobacterium lepraemurium.

C57BL/6 were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). At increasing time intervals after infection different isolated splenic cell subpopulations were tested for their ability to suppress the mixed lymphocyte reaction (MLR) of normal syngeneic mouse splenocytes. During the first 6 months after infection neither T depleted nor plastic adherent spleen cells from infected mice exerted a suppressive activity on the normal mouse allogeneic proliferative response. Conversely, splenic T cells from MLM infected mice exhibited suppressive activity as early as 2 months after infection. Attempts to characterize the Lyt phenotype of splenic suppressor T cells from 6 months infected mice showed that both Lyt 1+ 2- and Lyt 2+ enriched cell subsets possessed the ability to suppress the MLR of the normal mouse spleen cells and Lyt 1+ 2- T cells were shown to be more efficient suppressors than Lyt 2+ cells.

Animals↗
PubMed1983

Comparison between immunopotency tests and specific active or passive acquired resistance against Mycobacterium tuberculosis in mice induced with three different preparations of BCG pasteur vaccine.

Tests, exploring hallmarks of cell-mediated immunity (CMI), were used in order to compare immunogenecity of same numbers of viable units from three different preparations of BCG vaccine derived from the same strain. Specific and non-specific cellular immune responses were assessed by several tests including, active and adoptive acquired resistance to Mycobacterium tuberculosis, local and systemic granuloma formation. BCG persistence in the spleen, delayed type hypersensibility (DTH) to tuberculin, immunopotentiation of DTH to sheep red blood cells, increase resistance to Listeria monocytogenes infection and occurrence of non-specific in vitro immunodepression. The ranking order of the three preparations concerning the active specific acquired resistance to tuberculosis did correlate well the ranking established for all immunopotency tests used in our study, however differences in acquired resistance were small as compared to differences observed for immunopotency tests. Moreover, adoptive transfer of same number of lymphoid cells from immune donors gave a different ranking order; the well dispersed fresh frozen (FF) vaccine being more able to induce higher adoptive protection as compared to the mechanically dispersed preparations. All these results clearly demonstrated that BCG could not be considered as single entity and that the test based on acquired resistance to M. tuberculosis or in vivo or in vitro hallmarks of CMI cannot be used as standard procedures.

Animals↗
PubMed1981

BCG modulation of delayed type hypersensitivity, humoral response and acquired resistance after rabies vaccination.

The immunopotentiating action of BCG was evaluated in rabies. The maximum enhancing effect on delayed type hypersensitivity (DTH) was obtained 14 days after rabies immunization when different BCG vaccination schedules were tested in mice. A stable form of specific sensitization to rabies antigen under the modulation of BCG pretreatment was obtained. High concentrations of rabies antigen were found to be inhibitory for the DTH reaction. Levels of protection were evaluated in rabies vaccination after BCG modulation. One single injection of rabies vaccine in BCG pretreated mice was as effective as two injections of rabies vaccine in normal mice. However, in the latter, increase of protection was correlated with the levels of neutralizing antibody. On the other hand, the BCG pretreated mice, protection was not associated with a significant increase in antibody. Pretreatment with BCG alone influenced the outcome of fixed rabies as well as street rabies by enhancing the natural resistance to rabies infection.

Animals↗
PubMed1981

Comparative effects of carrageenan on systemic candidiasis and listeriosis in mice.

Carrageenan, a toxic substance for the mononuclear phagocyte system (MPS), increase drastically the susceptibility of mice against Listeria monocytogenes challenge but induces concurrently an increasing resistance against systemic candidiasis and granulocytosis. These results corroborate the minor role played by MPS and suggest that polymorphonuclear cells play a major role in non-specific resistance of mice against systemic candidiasis.

Animals↗
PubMed1981

Delayed-type hypersensitivity and acquired resistance to plague in mice immunized with killed Yersinia pestis and immunoregulators.

A simple reproducible footpad assay of delayed-type hypersensitivity (DTH) to Yersinia pestis was studied in mice immunized with 5 x 10(7) heat killed (HK) Y. pestis alone or in conjunction with Freund's complete adjuvant (FCA), cyclophosphamide (CY), BCG, or both CY and BCG. The footpad reaction elicited with 5 x 10(6) HK Y. pestis was shown to peak at 24 hr, was transferable with immune T lymphocytes but not with serum and had the classical DTH histology, The highest level of DTH occurred 6 or 8 days after immunization, according to the immunomodulator used, and immunized mice were therefore challenged with viable Y. pestis at this time. No correlation was found between DTH level and resistance of mice; only groups immunized under the potentiating effect of BCG used alone or with CY were significantly protected against Y. pestis. Control groups pretreated with BCG or BCG pretreated and immunized with a large dose of an unrelated gram negative bacterium were as susceptible to Y. pestis infection as normal mice. To promote this protective immunity, BCG and HK Y. pestis, must be injected in an area that drains to a common lymph node. No antibody to Y. pestis was found in immunized protected mice pretreated with BCG and CY and a very low antibody titre was found in immunized mice pretreated only with BCG. This serum was unable to confer resistance on recipient mice but immune cell transfer decreased the number of Y. pestis counted in the spleens of recipients 36 hr after challenge.

Animals↗
PubMed1980

In vivo detection of specific cell-mediated immunity in street rabies virus infection in mice.

In street rabies-infected mice, in vivo expression of delayed type hypersensitivity (DTH) measured by the footpad test was revealed by challenge with inactivated fixed rabies virus (RV). The use of BCG as an adjuvant cell-mediated immunity (CMI) was necessary for the production of significant DTH levels. Typical DTH kinetics were obtained, with a maximum at 24 h after the challenge. DTH was also found to be at highest levels 4 days after infection with street rabies virus. DTH could also be revealed with street rabies virus in RV immunized mice. Adoptive transfer of lymphoid cells from a street rabies infected donor to normal recipient mice was performed and DTH was tested with RV. Susceptibility of DTH to immunosuppression by cyclophosphamide treatment was also assayed in street rabies virus-infected mice and in adoptively-sensitized recipient mice. These results and the relationship between DTH and CMI in rabies infection and immunization are discussed.

Adjuvants, Immunologic↗
PubMed1979

Modulation by malaria infection of the induction of T lymphocyte-dependent delayed-type hypersensitivity and antibody formation to sheep erythrocytes in mice.

A profound alteration of the inductive phase of delayed-type hypersensitivity and antibody formation to SRBC was found in malaria infected mice when sensitization with this antigen was performed intravenously at a critical time of the disease, but not after subcutaneous immunization, suggesting a major role for the spleen in the mechanism of immunodepression.

Animals↗
PubMed1979

Kinetics of different specific immunological parameters after rabies vaccination in mice.

A significant protection to an intracerebral challenge of 70 mean lethal doses of a standard live rabies virus strain was obtained in BCG-pretreated mice or in normal mice which had been immunized with a single subcutaneous injection of a beta-propiolactone-inactivated rabies vaccine. Concomitantly, levels of delayed-type hypersensitivity (measured in vivo by the footpad test) and serum-neutralizing activity were evaluated at various times after immunization. All immune criteria were significantly augmented in the BCG-pretreated, rabies-immune mice as compared to normal, rabies-immune mice. However, peak levels of protection, delayed-type hypersensitivity, and serum-neutralizing activity did not occur at the same times. For instance, in the BCG-pretreated, rabies-immune mice, delayed-type hypersensitivity peaked on day 7, protection peaked on day 21, and serum-neutralizing activity peaked on day 60. In BCG-pretreated mice, which did not receive the rabies vaccine, positive delayed-type hypersensitivity, some protection, and serum neutralizing activity were observed 4 to 5 weeks after BCG pretreatment. The possible relationships between specific and nonspecific immunity provoked by rabies virus antigens, tissue culture cell-associated antigens (derived from the bovine fetal kidney cells in which the rabies virus was grown, and BCG are discussed.

Animals↗
PubMed1979

Immunological behavior after mycobacterial infection in selected lines of mice with high or low antibody responses.

Resistance and susceptibility to mycobacterial infection in the Biozzi high and low lines of mice which were genetically selected for their responses to heterologous erythrocytes have been found to be related to the innate ability of nonimmune macrophages to kill or inhibit the growth of the organisms during the first two weeks after infection and to their ability to mount specific and nonspecific immune responses. High antibody-producer mice were more capable of expressing cell-mediated immune parameters than low antibody-producer mice. A direct relationship was observed between the ability of bacteria (BCG vaccine) to multiply inside the reticuloendothelial system and the development of cell-mediated immunity, as measured by the delayed local reaction at the injection site, the lymphoproliferative response in the draining nodes, the tuberculin delayed-type hypersensitivity, the acquired resistance, and the adjuvant effect after BCG inoculation. In high line mice, apart from the inability of their macrophages to inhibit the early growth of bacteria, their lymphocytes in spleen and thymus were more capable of being stimulated in vitro by varying concentrations of living BCG. The data presented in this report are compatible with the hypothesis that a group of genes segregated in each line during the selective breeding controls the innate microbicidal activity.

Adjuvants, Immunologic↗
PubMed1979

In vivo antitumor activity of various forms of delayed-type hypersensitivity in mice.

Relationships among various forms of delayed-type hypersensitivity (DTH) and nonspecific resistance to Lewis lung tumor were studied in syngeneic and semisyngeneic mice. Only the tuberculin type of DTH obviated a virulent inoculum of 10(6) tumor cells. The Jones-Mote type of DTH, even modified by cyclophosphamide pretreatment, produced a significant local inflammatory reaction which was unable to destroy tumor cells. The antitumor effect of the tuberculin type was observed in BCG-or in Corynbacterium parvum-immune mice and also in sheep red blood cell-immunized mice, but only after the modulating effect of BCG. The antitumor activity of the DTH reaction was anatomically restricted and time related, and it required local persistence of specific antigen. A minimal number of bacteria, 1 times 10(6) living or heat-killed BCG organisms, were equally able to eradicate 10(5) tumor cells in BCG-immune mice. Biphasic effects on tumor growth were observed when systemic specific inflammatory reactions were elicited in BCG-immune mice. However, tumor-specific immunity was never observed, inasmuch as BCG-immune mice surviving injection of a mixture of BCG and tumor cells did not resist a second tumor cell challenge.

Animals↗
PubMed1979

Local immune response to Mycobacterium lepraemurium in C3H and C57Bl/6 mice.

Subcutaneous footpad inoculation of living M. lepraemurium (L.MLM) induced, in high responder C57Bl/6 mice, a local granulomatous reaction associated with the production of effector cells which stopped the multiplication of bacilli in the draining popliteal node with the concurrent development of 24--48 hr delayed type hypersensitivity (DTH). The thymus-dependent local reaction did not occur after the injection of heat-killed M. lepraemurium (HK.MLM) or after the inoculation of L.MLM in nude mice. However, HK.MLM injection interfered with the onset of the local reaction and enhanced acid-fast bacteria (AFB) counts in the draining node. In low responder C3H mice, L.MLM produced a local and delayed footpad swelling but no restriction of bacilli multiplication in the draining lymph node was observed. This unresponsiveness was not due to an overloading of the inoculum dose since doses ranging from 3 x 10(4) to 3 x 10(7) MLM did not produce any granulomatous local reaction as in C57Bl/6 mice. The injection of dead bacilli in the contralateral footpad of subcutaneously (s.c.) infected C3H mice revealed Arthus-like and 18--24 hr delayed reactions. When 10(6) L.MLM per mouse were injected intravenously (i.v.), systemic infection, measured in the spleen, was found to be less restricted in C57Bl/6 than in C3H mice. Moreover, in C57Bl/6 mice low doses of L.MLM injected i.v. delayed the local reaction at first, then enhanced footpad swelling and AFB counts in the draining nodes, indicating some acquired defect of peripheral immunity. When a high dose of L.MLM (2 x 10(8)/mouse) was injected i.v., C57Bl/6 mice died sooner than C3H mice, indicating certain discrepancies between local resistance and systemic susceptibility.

Animals↗
PubMed1978

Site of action of serum factors that block delayed-type hypersensitivity in mice.

When mice have been rendered anergic by a large intravenous dose of sheep erythrocytes, their inability to mount a delayed-type hypersensitivity (DTH) reaction is not due to an absence of mediator cells, for these can be detected in the spleen by cell transfer. Nor is it due to disappearance of accessory cells (monocytes) from circulation. The serum of anergic mice contains blocking factors which are more abundant after absorption with antigen. Such factors are unable to inactivate the mediators of DTH in vitro, nor do they suppress a DTH reaction when introduced locally into the reaction site. They are active, however, when given intravenously to systemically sensitized mice, provided that the sensitized animal has an intact spleen. If the spleen has been removed or the recipients of sensitized cells have been treated with cyclophosphamide before cell transfer, blocking factors are no longer able to suppress a DTH reaction. Reasons are given for the belief that suppression of DTH in animals undergoing a vigorous antibody response is due to the diversion of reactive cells from circulation to undertake an alternative role in antibody formation in the spleen.

Animals↗