Biomedical subjects

P H Lagrange

Publications and source records attributed to P H Lagrange.

155 records · Page 9Linked to original sources

PubMedDate not supplied

Mechanisms of T-cell unresponsiveness in leprosy.

We analysed the mechanisms of T-cell unresponsiveness to Mycobacterium leprae antigens and to unrelated antigens or T-cell mitogens in human leprosy and in an experimental model of murine infection by M. lepraemurium (MLM). In human leprosy, monoclonal antibodies OKT3, OKT4 and OKT8 were used to enumerate T-cell subpopulations within peripheral blood. Increased percentages of OKT8+ cytotoxic/suppressor cells were observed in untreated, non-reactional lepromatous patients. Conversely, lepromatous patients suffering from erythema nodosum leprosum, an Arthus-like phenomenon, exhibited a transient drop in the percentage of OKT8+ cells with a correlative increase in the proliferative response to T-cell mitogens. We studied the proliferative response to M. leprae of OKT4+ and OKT8+ cells isolated by a negative selection procedure using antibody-induced cytotoxicity plus complement. None of these subpopulations proliferated when incubated with M. leprae. In some patients, control treatment of mononuclear cells with complement alone induced the reappearance of a strong proliferative response to M. leprae, suggesting the existence of an active suppressor mechanism through soluble factors of an unknown nature. In MLM-induced murine leprosy, a progressive decrease was observed in the proliferative response to concanavalin A (ConA), and an early decrease in interleukin 2 activity in supernatants from ConA-stimulated spleen cells. Splenic T cells from MLM-infected mice transferred into naive recipients accelerated the local MLM growth in these recipients, suggesting that suppressor T cells may play a pathogenic role in the progression of MLM infection.

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PubMedDate not supplied

[BCG and leprosy].

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Adolescent↗

PubMedDate not supplied

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.

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PubMedDate not supplied

Influence of dose and route of inoculation and of mouse strain on the production of interleukin 2 in mice infected with Mycobacterium lepraemurium.

In order to evaluate the influence of route and dose of inoculation on interleukin 2 (IL2) production, C57BL/6 mice were infected either intravenously (I.V.) or subcutaneously (S.C.) with 10(5) or 10(8) Mycobacterium lepraemurium. The role of genetic factors on the production of IL2 during M. lepraemurium infection, was investigated in 7 inbred mouse strains (C57BL/6, DBA/2, F1 (C57BL/6 X DBA/2), DBA/1, BALB/c, CBA and A/J) after I.V. infection with 10(7) M. lepraemurium. At different times after M. lepraemurium inoculation, the number of AFB within the spleens of infected mice was counted and the ability of Con A-activated spleen cells to produce IL2 was studied. In S.C. inoculated C57BL/6 mice the increase in footpad thickness was measured during the progression of infection. After one month of infection heavily infected C57BL/6 mice (10(8) bacilli) showed an early and strong deficiency of IL2 production, regardless of the route of inoculation, whereas mice infected with a lower dose (10(5) bacilli) did not. In S.C. infected mice the decrease of IL2 production was observed when the footpad enlargement reached to the plateau phase. The data obtained from the numeration of AFB within the spleens of infected mice allowed to rank the infected mouse strains into 2 separated groups according to the pattern of the Bcg gene expression. An IL2 deficiency was only observed in C57BL/6, DBA/1, (C57BL/6 X DBA/2)F1 and DBA/2 infected mouse strains. No evident correlation could be shown between splenic IL2 activity upon Con A stimulation and the number of AFB recovered from the spleens of these 7 inbred mouse strains.

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PubMedDate not supplied

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.

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PubMedDate not supplied

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.

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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↗

PubMedDate not supplied

[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↗

PubMedDate not supplied

Systemic candidiasis in mice. I.--Correlation between kidney infection and mortality rate.

After intravenous inoculation of mice with large doses of living Candida albicans, the kidneys are the only organs where multiplication of fungi occurs. After systemic challenge performed with varying doses of yeasts, kidney infection shows an identical pattern during the first 12 h, independently of the magnitude of the inoculum. Destruction of parasites occurs during the first 3 h and then C. albicans begins to multiply. Death occurs when the number of microorganisms in the kidneys exceed 10(5) viable units and the time of death is correlated with renal infection measured 12 h after challenge. An identical correlation is found when mice are pretreated with an immunosuppressor or immunostimulants. No statistical significance is observed in counts of C. albicans in right or left kidney, in males or females, but a slightly higher total count and a lower mean survival time are noted in female mice. These results show that counting C. albicans in kidneys 12 h after systemic infection provides a rapid screening test. In addition, this fact taken with the mortality may explain the nature of the pathological processes which occur during systemic candidiasis in mice.

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PubMedDate not supplied

Delayed-type hypersensitivity to sheep red blood cells in selected lines of mice with high or low antibody responses.

Interline differences in DTH to SRBC which developed in high antibody producer (H/Ab) and low antibody producer (L/Ab) genetically selected lines of mice were observed after intravenous (IV) or subcutaneous (SC) sensitization. This interline difference was more marked in female that in male mice, and with the optimal dose for DTH sensitization. The kinetics of the local inflammatory reaction after local challenge, the development and decay of the 24-h DTH reaction tested at varying intervals after sensitization, were always statistically significantly higher in H/Ab than in L/Ab mice. This higher DTH was associated with a higher capacity of these mice to produce a secondary humoral response, and the more marked difference was observed for the production of 2-mercaptoethanol-resistant specific antibodies. Higher DTH reaction in H/Ab mice could not be explained by the participation of either B lymphocytes or humoral antibodies, since high dose (200 mg/kg) of CY injected before IV-SRBC, sensitization, in order to inhibit B-cell activation, did not alter the DTH-interline difference. Moreover, IV injection of specific antibodies from H/Ab immune mice did not enhance DTH in adoptively immunization L/Ab mice. Immune serum alone was not able to adoptively transfer DTH either in H/Ab or in L/Ab mice. Also, a low dose (40 mg/kg) known to inhibit T-cell suppression, injected before SC-SRBC sensitization, was not able to modify the DTH reaction in L/Ab mice. The persisting higher 48-h local inflammatory reaction in H/Ab mice after CY pretreatment was also related to a high blood monocyte rebound. When the afferent arc of the immune response to SRBC was studied in these mice, as tested by the lymphoproliferative response in draining popliteal node after footpad sensitization and by the evaluation of the ability of the T-activated cells located in these draining nodes to transfer locally an adoptively DTH reaction into naive recipients, it was shown that in immunized mice more specifically activated T cells were produced in H/Ab than in L/Ab mice. Moreover, the H/Ab recipients had a higher capacity to develop a local inflammatory reaction than the L/Ab recipients. The mechanisms of these observed interline differences are discussed.

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PubMedDate not supplied

[Effect of protein additives in mouse food on immune response to sheep red blood cells in mice (author's transl)].

Protein additives used in mouse food (fish meal, bovine blood meal, milk powder) interfere with the specific immune response induced with sheep red blood cells. Bovine blood meal reduces delayed type hypersensitivity (DTH) reactions and delays IgG production. Blood derivatives suppress mostly the central induction and not the peripheral expression of DTH since depression can be shown after systemic and not after subcutaneous immunization. The suppression of DTH is specific, it did not appear when DTH was produced with antigens presenting no antigenic cross-reactivity with protein additives (chicken red blood cells, tuberculin). This depressive effect was related neither to the presence of inhibitory serum factor nor to the production after immunization of specific antigen-antibody-blocking factor. Blood derivatives seem to act on the afferent arc of immune response especially on the splenic immunogenicity of the injected antigen to produce DTH.

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