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B Hurtrel

Publications and source records attributed to B Hurtrel.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

Time course and histological differences between sheep red blood cells and tuberculin DTH reactions in mice.

Delayed-type hypersensitivity (DTH) reactions induced with sheep red blood cells (1 X 10(8) SRBC/mouse) or with attenuated viable Mycobacterium bovis (4 X 10(6) BCG/mouse) inoculated subcutaneously and elicited, respectively, with SRBC or protein-purified derivative (PPD), were studied regularly in separate groups of outbred mice and compared during a period of one year following immunization. The present report shows the existence of two distinct types of DTH reactions. The SRBC type consists of a reaction which peaks consistently at 18 h, reaches a maximum 4 days after immunization, and decreases progressively until the fourth month. This local reaction, mediated by specific committed T cells as demonstrated by adoptive transfer experiments, was shown to consist mainly of a polymorphonuclear leukocyte infiltration. The PPD type consists of a local reaction which presents a different time course, the peak shifting from 18 to 42 h during the first two months after immunization, and which persists unchanged over a year after immunization. This second type of DTH reaction consisted of an early phase of polymorphonuclear infiltration followed by an increased number of mononuclear cells. Evidence is also given that the differences in the expression of these two types of DTH reactions depended neither upon the physical characteristics of the two antigens used for elicitation nor upon the nonspecific environmental modulating activity of BCG, since soluble SRBC protein and heat-killed BCG cells elicited the same distinct types, and the two distinct DTH reaction types could be elicited in mice immunized with both BCG and SRBC.

Animals↗
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Dissociation between cell-mediated immunity and acquired resistance in systemic murine candidiasis.

Mice immunized with 10(7) heat-killed (HK) Candida albicans injected subcutaneously with or without BCG, used as an immunoadjuvant, were able to develop strong significant delayed-type hypersensitivity (DTH) against C. albicans but without any increase in specific resistance, as measured by median survival time and enumeration of yeasts inside target organ such as lungs, liver, spleen and kidneys after an intravenous (i. v.) challenge of 1 X 10(6) live C. albicans. Concomitant activation of the mononuclear phagocytic system, measured in vivo by increased resistance to L. monocytogenes, was shown to be induced in immune mice challenged i. v. with 1 X 10(6) HK C. albicans. These results are in favour of a clear distinction between DTH and acquired resistance to systemic candidiasis, even in the presence of specific activation of macrophages.

Animals↗
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Vaccines against mycobacteria and other intracellular multiplying bacteria.

As the prototype of a vaccine against mycobacterial infection, the BCG (bacille bilié Calmette et Guérin) has been used against tuberculosis for more than 60 years. It is the only live attenuated vaccine used on humans in more than 182 countries or territories in the world, and very few changes have been made in its fabrication and distribution, except for the production of lyophilized seed-lots. However, its history is marked with controversies concerning its innocuity and efficacy. While BCG safety is no longer a matter of debate, the question of its effectiveness is still pertinent, and results in several controlled trials have shown great variability (from 0 to 80%). The studies of different variables involved in such results have shown statistical bias, and numerous factors are involved in the highly complex interrelationships between the host, the pathogen and environmental factors. World-wide research is now being conducted under the auspices of the World Health Organisation, in order to gain further knowledge of the immunology of tuberculosis and leprosy. Such results are aimed at understanding variations in BCG efficacy and producing strategies for developing new vaccines and alternative methods for prophylaxis and diagnosis. Concerning human infections due to other facultative intracellular multiplying bacteria, there are relatively few vaccines which are able to give long-lasting and efficient protection. Some controversy remains as to the live attenuated mutant GalE S. typhi Ty21a, and there is hope for the new insoluble phenol extract from Brucella abortis, strain B19. Further research is necessary on the others, for instance, Listeria monocytogenes, Chlamydia trachomatis and Legionella sp.

Bacterial Infections↗
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Target cells during early SIV encephalopathy.

Early encephalopathy was studied in rhesus macaques in the first month following intravenous (i.v.) infection with SIV-mac-251. Histopathological analysis of brain tissues showed slight gliosis, associated with perivascular infiltrates and occasional glial nodules. Immunophenotyping of brain tissue showed microgliosis with expression of MHC class II molecule and macrophage infiltration associated with a few lymphocytes. At the early stage of infection, most infected cells were perivascular, suggesting that infiltrating cells are the main route of entry of the virus into the brain. Using combined immunochemistry and in situ hybridization, it was shown that these infected perivascular cells were mostly macrophages. Later, SIV infected a limited number of cells expressing the same CD68 monocyte/macrophage/microglia marker. Using different genome probes, hypotheses concerning SIV RNA expression during early brain infection were tested. It was shown that the latent brain infection was not due to a complete transcription block, but rather to productive replication of SIV at a low level in a small number of target cells in the brain. Injection of SIV by the intracerebral (i.c.) route induced the same slight encephalitis as observed in i.v. inoculated animals. The very small number of infected cells found around the site of i.c. inoculation suggests that resident microglia are poorly susceptible to infection by SIV.

AIDS Dementia Complex↗
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Early events in lymph nodes during infection with SIV and FIV.

To elucidate the initial pathogenic events in lymphoid organs, the major reservoir of virus in HIV infection, follow-ups of viral load, pathological changes and target cells were performed in the rhesus macaque SIVmac251 model and in the cat FIV model. Lymph nodes (LN) obtained from animals sacrificed at early time points following experimental inoculation were analysed by in situ hybridization for virus load and by combined immunohistochemistry and in situ hybridization for virus cellular tropism. In the SIV model, the LN presented a high viral load at 7 days post inoculation (p.i.); at this stage, macrophages and T4 lymphocytes were identified as the target cells of the virus. A shift in the pattern of viral infection was observed at 2 weeks p.i., with a concentration of viral RNA in follicular dendritic cells (FDC) in the germinal centres of the developing lymphoid follicles. This FDC-associated virus persisted at high levels for 2 months p.i. in the FIV model, the number of infected cells detected in LN was very low compared with that found in the SIV model, and a similar role played by FDC was found.

Animals↗
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Signs of Kupffer cell involvement in productive simian immunodeficiency virus infection in monkey liver.

The livers of 21 rhesus monkeys inoculated with SIVmac251 were examined at 4 days to 39 months after infection. SIV antigens were detected in the cytoplasm of Kupffer cells (KC), macrophages and lymphocytes in two-thirds of the livers tested. The number of cells containing viral proteins substantially increased during the development of the disease, and KC were the main cell type displaying SIV proteins at an advanced stage of infection. Mature and immature lentiviral particles were found in cytoplasmic vacuoles or associated with worm-like structures in KC, indicating that SIV replication could occur within resident liver macrophages. Another sign of the permissiveness of KC was the formation of multinucleated giant cells within the hepatic sinusoids. Some of these cells containing 3-6 nuclei still retained ultrastructural features of KC. Most of them contained a high quantity of viral particles. Numerous lymphocytes displaying signs of apoptosis were taken up by KC, especially at the beginning of infection. Hyperplasia and hypertrophy of KC were noted in the course of SIV disease in the liver. The present data indicate that KC can be infected in vivo and may serve as a reservoir for SIV during the progression of the disease.

Animals↗
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Kinetics of primary SIV infection in lymph nodes.

The very early stages of SIV infection in lymph nodes of rhesus monkeys were characterized by in situ hybridization. Massive viral replication was detected in macrophages and lymphocytes during the first week of infection. In a second phase, SIV RNA concentrated in the developing germinal centers, and colocalized with the follicular dendritic cells. The down-regulation of the viral load in lymph nodes varied depending on the animal, indicating early differences in the susceptibility to SIV infection.

Animals↗
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[Delayed local reaction (DLR) after BCG vaccination in mice. I.--Description (author's transl].

Mice injected subcutaneously in the hind footpad with BCG vaccine subsequently develop a local reaction. This local reaction could be divided into three stages: a first characterized as an acute inflammatory reaction, a second as an active granulome formation, and a third as a chronic long lasting inflammatory reaction. The second stage is mainly formed by the appearance of a typical histiolymphocytic granuloma. The intensity of the delayed local reaction (DLR) is measured by the swelling of the injected footpad. This reaction does not occur after injection with irradiated (gamma or UV) BCG in normal mice, nor after injection of living BCG in Nude mice, indicating a T-cell immune response which develops during the in vivo multiplication of this intracellular bacteria. When the lymphoproliferation response in draining node was measured, a direct correlation was found with the intensity of the DLR, and the 125IUdR incorporation into DNA after injection of living BCG or after an irradiated BCG inoculation. The intensity and the rapidity of the onset of this DLR depend upon the dose of viable BCG inoculated in the mouse. When the DLR reached its peak, a linear dose relationship was observed in C57Bl/6 and in NCS mice.

Animals↗
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[Delayed type hypersensitivity reactions to "Candida albicans" in mice (author's transl)].

Mice injected intravenously (IV) or subcutaneously (SC) with living Candida albicans developed subsequently delayed-type hypersensitivity (DTH) which was measured in vivo by the footpad test after injection of 10(6) heat killed C. albicans (HKC.a.). Compared to systemic injections, SC immunizations with living C.a. gave higher levels of DTH, and lethality was absent. Subcutaneous injections of hundred time more doses of HKC.a. were also able to produce in normal mice a DTH reaction elicited with HKC.a. or with C.a. soluble extracts, but not with candidine. Intraperitoneal injections of varying doses of HKC.a. or subcutaneous injections of varying doses of C.a. soluble extracts failed to produce significant DTH. High levels of sensitization can be induced by using cyclophosphamide or BCG or both pretreatment before immunization, which seems to indicate immunomodulating factors for induction or expression of DTH in normal mice after injections of HKC.a. Kinetics of the local reaction elicited with HKC.a. fulfull usual criteria of DTH in actively immunized mice after CY pretreatment or not, and in passively immunized mice after systemic or local transfer of spleen cells from actively immune donors. Serum from same group of donors was unable to transfer DTH.

Animals↗
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[Effect of bacterial phospholipidic extract (EBP) on the immune response in mice toward sheep red blood cells (author's transl)].

Injection in mice of bacterial phospholipidic extract (EBP) stimulates immune responses to sheep red blood cells (SRBC). Immunostimulation was observed mostly for antibody response and to a less extent for delayed-type hypersensitivity (DTH). The adjuvant effect of EBP is dependent on several factors: dose, route and time. Maximal activity was found when mice received 100 to 200 microgram of an intravenous injection of EBP, twenty-four hours before systemic immunization with optimal doses for antibody or DTH response. Subcutaneous injection of EBP did not modify the cellular or humoral immune response to SRBC inoculated subcutaneously in the same or in a different site of EBP. Adjuvant action of EBP was different of those of endotoxin, since the later suppresses the DTH response to optimal dose of SRBC, this effect being abolished with cyclophosphamide pretreatment. EBP inoculated intravenously suppressed the local reaction of a DTH adoptively transferred with immune spleen cells. These results taking together seem to indicate a preferential role of EBP on the accessory cells in the induction or expression of the immune response to SRBC.

Adjuvants, Immunologic↗
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[Inflammation and resistance of mice infected by "Candida albicans" (author's transl)].

An inflammatory reaction induced by the subcutaneous injection of talc embedded in a gel calcium phosphate increased resistance of mice challenged intravenously with Candida albicans. The relationship between the absolute number of polymorphonuclear phagocytes in the blood and this protective effect seems to indicate a major role of polymorphonuclear leukocytes following inflammation.

Animals↗
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The influence of BCG vaccination on murine leprosy in C57BL/6 and C3H mice.

Cross-reactivity between Mycobacterium lepraemurium (MLM) and BCG vaccine was found and evaluated in vivo, in C57BL/6 mice, in terms of delayed-type hypersensitivity, local granulomatous response at the injected site and limitation of growth of the challenge inoculum in the draining node. Cross-reactive specific protection and local reactivities were transferred in syngeneic normal recipients by means of non-adherent lymphoid cells from immune donors. When BCG vaccine was injected either intravenously or subcutaneously in C57BL/6 and in C3H mice, it was able to induce resistance to local infection with living MLM in both strains, but no alteration of the local granulomatous reaction (equivalent to local specific immune response) was observed in C3H mice, as compared to the control. When mice were immunized with one or two injections of heat-killed MLM after the immunomodulating effect of BCG vaccination, better immunization was not achieved. In order to test the presence of strain-related immunosuppressive mechanisms, mice were cyclophosphamide-treated during the immunization process. As expected, higher specific DTH reactions were obtained in both strains, but with only a slight increase of the protective mechanism. Protection was always higher in C57BL/6 than in C3H mice. The specific and non-specific immune responses to BCG vaccine were then evaluated in both strains with different parameters: in vivo lymphoproliferative response in the draining node, delayed local granulomatous reaction at the injected site after a subcutaneous injection, increase in spleen index, kinetics of the immunopotentiation to a thymus-dependent antigen (sheep red blood cells) after a single intravenous injection of BCG. A striking interstrain difference was observed; C57BL/6 mice were able to mount a more rapid and marked immune response as compared to C3H mice (which only developed a delayed and slight response). Moreover, these differences were associated with the fact that BCG did not seem to multiply properly in C3H mice during the first two weeks after inoculation. Thus, it was concluded that higher natural resistance to pathogens and cross-reactive preimmunization with related microorganisms can interfere with the artificial immunization when living microorganisms are used. Implication for vaccination to mycobacterial infection (tuberculosis and leprosy) are discussed.

Animals↗
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Systemic candidiasis in mice. II.--Main role of polymorphonuclear leukocytes in resistance to infection.

Cyclophosphamide (CY) increased whereas the talc embedded in a calcium phosphate gel (TCP) decreased the susceptibility of mice to systemic candidiasis estimated by measuring mean survival time and "renal infectivity" 12 h after challenge. Transfers of plasma from CY- and TCP-treated mice did not modify cnadidiasis susceptibility of recipient mice. Granulopenia and granulocytosis induced respectively by CY and TCP were significantly correlated with susceptibility or resistance to candidiasis. Nevertheless, TCP produced significant reticuloendothelial stimulation which could be also correlated with TCP protection. Reticuloendothelial stimulation with associated granulopenia in TCP-CY-treated mice gave protection against Listeria monocytogenes challenge but not against Candida albicans. Thus, blood polymorphonuclear leukocytes seem to play the main role in natural resistance of mice to candidiasis. This was corroborated after injection of immunostimulants; a good correlation was found between C. albicans resistance and the induced granulocytosis.

Animals↗
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Immunological mechanisms controlling mycobacterial infections.

After a brief review of the present knowledge about cell mediated immunity mechanisms involved in controlling mycobacterial diseases, variations of the immune responses to mycobacterial diseases in man and in experimental animals models are described. Related factors involved in the variations of the BCG vaccination effectiveness against human tuberculosis are presented according to present hypotheses on varying potency of BCG strains and influence of previous sensitization with non tuberculous mycobacteria. Also new hypotheses concerning qualitative differences in immune responses to mycobacteria in humans are discussed in association with information suggesting that tuberculosis, as other granulomatous chronic infectious diseases, is a disease in which an immune spectrum can be described with a significant modulation of T and B lymphocyte mediated responses. Evidence obtained in murine experimental models, using BCG infection in inbred and recombinant mice, demonstrated the existence of at least two genes which are able to control the induction and expression of CMI after mycobacterial infection. One of them, being not linked with the major histocompatibility complex gene (non H2), controls the natural non specific activity of the mononuclear phagocytic system and the other, linked with H2 complex, is able to modulate the level of CMI in responsive mice. Collective or individual antituberculosis strategies must be reconsidered following this finding.

Animals↗
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Residual immunogenicity of irradiated spleen cell suspensions after a single intravenous injection of sheep red blood cells in mice.

Studies were carried out to characterize the residual immunogenicity located in spleen cells of mice after one single intravenous injection of SRBC. An in vivo system was applied for initiation and expression of the immune response consisting of one intraperitoneally injection of spleen cell suspension from SRBC-injected mice in separate groups of recipients in which DTH and secondary humoral response were measured, respectively: six days or four days after the transfer of irradiated spleen cell suspension, the separate groups of recipients being either pretreated with cyclophosphamide (200 mg/kg) or primed with 5 X 10(5) SRBC. The residual immunogenicity was found to be located in a population of radio-resistant (10,000 rads) adherent spleen cells. The same population derived from naive mice injected together with the native antigen did not modify the immune response as compared with those induced by the antigen alone. Furthermore, irradiated spleen cell suspensions from SRBC-injected mice were not able to transfer adoptively DTH sensitivity in naive recipients. Accordingly to the test used to evaluate the residual immunogenicity, it was found that the kinetics of residual immunogenicity able to induce DTH was different from those which stimulate the secondary humoral response. Furthermore, it was found that distinct variations of residual immunogenicity for DTH and antibody formation were induced by varying host manipulations, such as non-specific stimulation of the reticulo-endothelial system, specific activation of T cells involved in DTH or helper function or induction of a state of anergy. It appears, therefore, that the same population of radio-resistant adherent spleen cells are able to induce an immune response and to dispatch information to cells involved in DTH or those involved in antibody synthesis. Moreover, depending upon conditions of immunization, varying subsets of T cells are able to modify the dispatching function of these cells in the processing or presentation of antigen to committed or non-committed lymphocytes.

Animals↗
PubMedDate not supplied

[Delayed local reaction (DLR) after BCG vaccination in mice. II.--Correlations with the immune response (author's transl)].

The occurrence and intensity of the DLR were correlated with different parameters of the specific and non-specific immune response induced by the inoculation of viable BCG into the footpad. A good parallel exists between the occurrence of the DRL and effector mechanisms which tend to limit the growth of BCG in the draining node, and also with the appearance of tuberculin hypersensitivity measured in vivo by skin-test. Nonspecific immunity induced in mice after subcutaneous BCG injection was measured using the relative spleen weight, and this correlates well with the onset of the DLR. Delayed type hypersensitivity (DTH) to varying doses of sheep red blood cells (SRBC) injected intravenously in normal or in subcutaneously BCG-pretreated mice indicated a functional increase of the reticuloendothelial system activity, 14 days after BCG injection. Lastly, the degree of adjuvanticity induced by BCG vaccination to DTH against SRBC which were injected in the same footpad, was strictly correlated with the kinetics of the DLR. The value of measuring DLR in mice is discussed concerning the evaluation of the immunogenicity of BCG vaccines and slso the host's capability to mount an immune response after subcutaneous BCG injection.

Adjuvants, Immunologic↗
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[Inflammation and resistance of mice against "Plasmodium berghei" (author's transl)].

An inflammatory reaction induced in mice by a subcutaneous injection of magnesium silicate embedded in a calcium phosphate gel is followed by an increased resistance against Plasmodium berghei. The occurrence of this increased resistance against Plasmodium berghei. The occurrence of this increased resistance is related to the time elapsed between the induction of the inflammatory process and the infection. The delayed mortality is correlated with a slowed development of parasitemia. It is hypothesized that the protective effect may be related to the capacity of the inflammatory reaction to promote in mice both specific and non-specific antiparisitic immune responses.

Animals↗