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P H Lagrange

Publications and source records attributed to P H Lagrange.

At least 127 records · Page 7Linked to original sources
PubMed1978

Delayed-type hypersensitivity to rabies virus in mice: assay of active or passive sensitization by the footpad test.

With a purified beta-propiolactone-inactivated rabies virus, a significant increase in footpad swelling was elicited in normal or in BCG-pretreated mice after immunization with varying doses of rabies vaccine. These footpad reactions were shown to peak at 24 h and to be associated with an infiltration of newly formed blood monocytes demonstrated by histology and [125I]deoxyuridine labeling. A relationship between the lymphoproliferation and the degree of sensitization is described, and the susceptibility to cyclophosphamide treatment is also examined. Adoptive transfer of specific reactivity to normal recipient mice with immune lymphoid cells, but not with immune serum, was demonstrated, and the results represent another argument for a cell-mediated immunological mechanism.

Animals↗
PubMed1978

Delayed type hypersensitivity in mice immunized with inactivated rabies virus.

Evidence of the DTH reaction is in agreement with in vitro observation done with the lymphoblast transformation test in rabbits (5,8) or with the cytotoxicity test in mice (7). The footpad test (FPT) fulfilled all criteria of DTH. A maximum swelling at the injection site was observed 24 h after challenge. FPT could not be transferred by immune serum. But both local and systemic transfer of dissociated spleen cells or lymph node cells sensitized recipient mice to the FPT. A lymphoproliferative response in the draining lymph node was observed after injection of RV, coinciding with the appearance of circulating cells mediating DTH and this response is not dependent upon a B-cell regulatoring mechanism (3). Evaluation of vaccines in vivo by specific DTH reaction is of interest for testing the cell-mediated immunity of these vaccines.

Adjuvants, Immunologic↗
PubMed1975

A stable form of delayed-type hypersensitivity.

An antigen dose below the level needed to provoke an antibody response produces in mice a persistent, but minor degree of delayed-type hypersensitivity (dth) to sheep red blood cells. The DTH is unstable. It is erased by larger doses of antigen and cannot be built upon by further antigenic stimulation. The much higher levels of DTH resulting from immunization under the modulating influence of cyclophosphamide (CY) or BCG persist under strong secondary antigenic stimulation, though the former is subject to partial suppression unless CY is used to prevent the secondary humoral response. The DTH produced by a BCG-modulated primary response is not subject to this suppressive effect of a secondary antibody response. In this case the anamnestic T-cell response is very brisk and cannont be potentiated by giving CY at the time of the secondary antigenic stimulus. This effect is not due to the modulating influence of a residual BCG infection. It results from a permanent change induced during the primary response. The mediator cells formed under the influence of BCG are apparently resistant to inhibition by blocking serum containing immune complexes. Even the actively dividing T cells which are susceptible to vinblastine, and most readily blocked in the absence of BCG, are highly resistant to blocking by immune complexes. It is not clear whether these cells are intrinsically different or whether their insensitivity to blocking results from features peculiar to the humoral response that accompanies a BCG-modulated primary response. The mediator cells produced by both BCG- and CY-modulated responses become vinblastine resistant, relatively insensitive to humoral blocking factors, and capable of surviving in a functionally active form in syngeneic recipients with an apparent half-life of about 50 days. There were indications, however, that their effective life-span may be greatly extended in some circumstances by persisting antigenic stimulation; and in the case of BCG-modulated immunity the prevailing level of T-cell activity can be greatly augmented by a further antigenic stimulus without the necessity for renewed exposure to BCG.

Animals↗
PubMed1975

Effects of bacterial lipopolysaccharide on the induction and expression of cell-mediated immunity. II. Stimulation of the efferent arc.

The delayed-type hypersensitivity (DTH) produced by subcutaneous or intravenous immunization of mice with sheep red blood cells (SRBC) is mediated by T cells in cooperation with accessory cells (monocytes). Different effects of bacterial lipopolysaccharide (LPS) on this T cell activity were found at different stages of the immune response. a) T cell activity was enhanced by LPS given 1 to 3 days after sensitization. Enhancement, which was most marked when treatment was given on the 2nd day of the immune response, did not occur unless LPS was introduced into a site that drains to the responding lymph node. This stimulatory effect was dose dependent. b) A similar effect on the response to intravenous immunization caused DTH to appear transiently in mice given a T cell-blocking dose (10-9) of SRBC. c) DTH was suppressed by LPS given at the height of the T cell response (day 4). This effect, which was short lived and reversible, was due to the action of LPS on the accessor cells needed for the expression of DTH. Treatment of recipients with LPS completely blocked the adoptive transfer of DTH to both normal and spenectomized mice. The ability to react was regained slowly, but it returned promptly to splenectomized recipients. LPS has clearly more than one effect on the expression of cell-mediated immunity because it affects specific and non-specific mediator cells in different ways.

Animals↗
PubMed1975

Effects of bacterial lipopolysaccharide on the induction and expression of cell-mediated immunity. I. Depression of the afferent arc.

Bacterial lipopolysaccharide (LPS), being a B cell mitogen, enhances antibody production. When given prior to an injection of sheep red blood cells (SRBC) it caused a premature but not significantly increased production of antibody forming cells in regionally stimulated lymph nodes. There was a corresponding depression of T cell activity, as measured by the relative levels of delayed-type hypersensitivity (DTH) in normal and LPS-treated mice. Although LPS also induced hyperplasia of the reticuloendothelial system, and a consequent reduction in the effective antigenic dose of SRBC, this was not the reason for the reduced level of T cell activity. The opposing effects of LPS on T and B cell responses was due to premature inhibition of the T cell response by an accelerated production of antibody. This caused an earlier onset of the inhibitory mechanism which regulates the T cell response and is specific for the inducing antigen.

Animals↗
PubMed1974

Restoration of cell-mediated immunity to animals blocked by a humoral response.

The T cells which mediate delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) are blocked by a normal humoral response and cannot be made to function by further immunization. They can be rescued to some extent by treatment with immunopotentiating agents such as cyclophosphamide (CY) which suppresses the antibody response selectively, or by BCG which interferes with the action of serum blocking factors. These two agents together can restore cell-mediated immunity completely, but a further antigenic stimulus is needed to reestablish DTH in mice blocked by a long period of continuous exposure to SRBC.

Animals↗
PubMed1974

Potentiation of T-cell-mediated immunity by selective suppression of antibody formation with cyclophosphamide.

Delayed-type hypersensitivity (DTH) appears in mice immunized with less than an optimal immunogenic dose of sheep red blood cells (SRBC), but is blocked progressively as antibody production increases in response to larger doses of SRBC. Treatment with cyclophosphamide (CY) was shown to release T cells from this inhibitory influence of the humoral response, and cause enhancement of DTH. The magnitude of this enhancing effect on T-cell activity was markedly dependent on the time of treatment relative to the time of immunization, and on the time chosen for measuring DTH. The reasons for these pronounced effects of timing are threefold: (a) CY given before antigenic stimulation has a long-lasting effect on antibody formation, but no apparent effect on the precursors of activated T cells. (b) After antigenic stimulation, T cells also become susceptible to CY. (c) The production of a nonspecific participant (monocyte) in the DTH reaction is also suppressed by CY, though the supply of circulating monocytes is not immediately affected by the drug. The differential effect of CY on T and B lymphocytes depends on the differing physiological states of the majority of cells that make up these two populations. The former are resting cells that are insensitive to CY until exposed to specific antigen, while the latter are drawn from a rapidly replicating precursor pool and are susceptible to CY at all times.

Animals↗
PubMed1974

The modifying effect of BCG on the immunological induction of T cells.

The inhibition of activated T cells by products of the humoral immune response is almost abolished by systemic infection with BCG. As a result, BCG-infected mice develop very high levels of delayed-type hypersensitivity (DTH) in response to doses of sheep red blood cells (SRBC) that cause complete suppression of DTH in normal mice. This systemic effect of BCG is dose-dependent, and lasts for about 3 wk. Its main effect is to counteract the inhibition of T cells by products of the humoral response. As a result, and in contrast to the T-cell-potentiating effects of cyclophosphamide (CY) which depend on a diminished production of antibodies, increased levels of DTH in BCG-infected mice are associated with increased antibody production. Since BCG and CY act in different ways, their effects are additive. Very remarkable levels of DTH are achieved when they are used in combination.

Animals↗
PubMed1974

Influence of dose and route of antigen injection on the immunological induction of T cells.

Delayed-type hypersensitivity (DTH) develops in the absence of an adjuvant when mice are injected intravenously or subcutaneously with an appropriate dose of sheep red blood cells (SRBC). The optimal intravenous dose of 10(5) SRBC (in CD-1 mice) produces maximum DTH which decays exponentially from its peak on day 4. Increasing the dose of SRBC reduces and eventually abolishes all evidence of DTH. DTH fails to reappear in respose to secondary stimulation except in splenectomized mice in whom the development of DTH is not suppressed, even by massive doses of SRBC. Hence the suppression cannot be due to antigen as such. The optimal dose of SRBC for sensitization by footpad inoculation is 100-fold higher (10(7) SRBC in CD-1 mice), but even 10(9) SRBC do not block the induction of DTH by this route of immunization. A blocking dose of SRBC, given intravenously 1 day before footpad inoculation, completely suppresses cell proliferation in the draining lymph node, prevents PFC production there, and blocks the induction of DTH by a sensitizing dose of SRBC. If given 1 day after footpad sensitization, intravenous antigen has little effect on the cellular response in the regional node but DTH is still completely suppressed. Blocking of induction and expression may depend, therefore, on different mechanisms.

Animals↗
PubMed1974

Feedback inhibition of specifically sensitized lymphocytes.

An explanation was sought for the fact that delayed-type hypersensitivity (DTH) does not normally occur in response to T-cell-dependent antigens unless an adjuvant is used. But when sheep red blood cells (SRBC) were administered intravenously DTH did appear, provided that the dose of antigen was less than that required to give a maximum antibody response. Animals in which T-cell activity had been blocked by a large dose of antigen could not be sensitized adoptively, and their spleen cells failed to transfer DTH to normal recipients. The serum of blocked animals partially inhibited the induction of DTH, and after absorption with SRBC its blocking activity increased substantially. Moreover, absorbed serum inhibited DTH in previously sensitized animals, but it did not inhibit the proliferative response to SRBC in peripheral lymph nodes or reduce the number of plaque-forming cells produced therein. On the contrary, the hemagglutinating titer was actually increased by blocking serum even though DTH was totally suppressed. It is concluded that a product of the interaction between antigens and antibody blocks the activated T cells which mediate DTH without interfering with helper cells.

Animals↗
PubMedDate not supplied

TNF alpha, IL-1 beta and IL-6 plasma levels in neutropenic patients after onset of fever and correlation with the C-reactive protein (CRP) kinetic values.

Cytokines, especially tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) play an important role in the genesis and progression of the septic shock syndrome. We performed a study monitoring levels of these three cytokines in ten neutropenic oncology patients in whom an infectious syndrome was suspected. A comparison was made with a population of nine non-neutropenic patients on the intensive care unit. Unfortunately the results of this study do not allow specific profiles to be established for each cytokine in the populations studied. Levels of IL-6, TNF alpha and IL-1 beta were not statistically higher in the non-neutropenic patients when compared with the neutropenic group. However, the highest IL-6 levels were observed for four non-neutropenic patients, three of whom died. High levels of C-reactive protein (CRP), haptoglobin and fibrinogen were found, reflecting the inflammatory status of each patient. CRP levels were higher in the non-neutropenic patients and correlated with IL-6 levels, indicating the importance of CRP determination in this group of patients.

Acute-Phase Proteins↗
PubMedDate not supplied

Immunomodulation with P40, an insoluble delipidated fraction of Corynebacterium granulosum. I.--Immune response to sheep red blood cells.

The immunological responses to sheep red blood cells (SRBC) were evaluated in mice in order to study the immunomodulating effects of an insoluble fraction of Corynebacterium granulosum, designated P40. A single intravenous (IV) injection of 50 micrograms or more of P40 was able to stimulate the reticulo-endothelial system, as measured by the spleen index. A single IV injection of 250 micrograms of P40, given seven days prior to IV sensitization of groups of mice with varying doses of SRBC, was able to amplify both humoral and cellular immune responses. Lower doses of P40 given subcutaneously (SC) were able to potentiate delayed-type hypersensitivity (DTH) to SRBC. Potentiation depends on the route, dose and time of the P40 injection in relation to the time and route of sensitization. A bimodal activity of P40 was observed: one peak was noted with SRBC were mixed with P40, and a second peak occurred when P40 was injected at the same site four to five days prior to immunization. Maximal potentiation was achieved when SRBC were introduced SC together with 5 micrograms of P40. DTH reached a higher level in animals immunized under the influence of P40; however, the kinetics of the development and decay of DTH were the same in treated and non-treated mice. Immunopotentiation was demonstrated by passive transfer: using the same number of spleen cells from treated or non-treated immune mice, higher DTH reactions were observed in normal recipients when they received spleen cells from P40-treated donor mice. Immunopotentiation seemed to act by increasing the number of committed lymphocytes and not by augmenting the number of accessory cells, since adoptive transfer of DTH by immune cells was not different in normal or P40-treated recipients.

Adjuvants, Immunologic↗
PubMedDate not supplied

Immunomodulation with P40, an insoluble delipidated fraction of Corynebacterium granulosum. II.--Specific immune responses of the host.

Mice immunized subcutaneously in the footpad with P40, an insoluble fraction extracted from delipidated heat-killed Corynebacterium granulosum, developed systemic mechanisms which depended on the generation of a state of systemic cellular hypersensitivity to P40 antigens. An injection of P40 into the footpad resulted in a striking increase in cell division in the draining lymph node, the development of a state of specific systemic delayed type hypersensitivity and a systemic increase in the bacterial capacity of the host macrophages. The footpad containing the immunizing injection of P40 also reflected the generation and decay of host sensitivity. Whereas the expression of 24-h skin sensitivity reactions to the eliciting injection of P40 antigens peaked at about day 6, the maximal increase of the local granuloma reaction peaked at about day 14, the latter representing a cumulative reaction. These local reactions and systemic hypersensitivity did not develop in congenitally athymic Nude mice. Time- and dose-dependent variations were detected in different strains of mice. Systemic hypersensitivity could be transferred to normal recipients with lymph node cells or spleen cells but not with serum from P40-immunized donors. All the results produced in this report indicate the distinct possibility that the systemic hypersensitivity which developed after P40 sensitization was based on cell-mediated responses to P40 antigens.

Adjuvants, Immunologic↗
PubMedDate not supplied

Vaccination of mice against Leishmania mexicana amazonensis with microsomal fraction associated with BCG.

Attempts to develop a satisfactory vaccine against New World cutaneous leishmaniasis have been made with varying success. We found that in mice, pretreated subcutaneously with 2 X 10(6) BCG organisms 2 weeks prior to immunization at the same site with as low as 10 micrograms of a microsomal preparation (Pol-F) of Leishmania mexicana amazonensis, a profound alteration was observed in the course of infection produced by inoculation of virulent amastigotes of the same strain. The BCG-Pol-F vaccine preparation was consistently shown to have a protective capacity associated with larger classical cellular immune response (skin test) and higher specific antibody titres in response to leishmanial challenge dose (1 X 10(6) amastigotes/mouse).

Animals↗
PubMedDate not supplied

Chagas' disease: enhancement of systemic inflammatory reaction in cyclophosphamide treated mice.

An explanation was sought for the fact that an enhancement of myocarditis occurs when Trypanosoma cruzi infected mice is treated with cyclophosphamide (CY). Several schedules were tested in mice and two polar models were achieved--one presenting parasite exacerbation without inflammatory reaction and the other presenting only cellular infiltrate in function of timing and different dosage of drug. In those receiving the drug after infection, an enhancement of the parasite load was detected and it was associated with an inflammatory reaction when mice were treated every other day with low doses of CY (3 mg/kg), but such inflammation was not present if a single dose of 200 mg/kg was used 5 days after infection. On the other hand, in schedules using 200 mg/kg of CY 2 days before infection an enhancement of myocarditis was observed on day 12 post infection, but this was not associated with parasite proliferation. Finally when employing a single intermediate dose of 40 mg/kg, a parasite load as well as a myocarditis enhancement was observed. A correlation between blood monocytes rebound and the intensity of myocarditis has been observed, and the varying time of drug injection suggested that this cellular infiltrate modulates the parasite load. If the immunosuppressive period of the drug occurred during parasite tissue invasion, parasite load amplification would occur without myocarditis. This was achieved using a single dose (200 mg/kg) of CY five days after infection, since monocytosis occurs 7-8 days after drug injection, allowing for parasite multiplication in tissues. The present data bring a strong suggestion that the modulation of myocarditis and parasite load are directly correlated with the leukocytes rebound occurring after the depression period promoted by CY treatment.

Animals↗