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C Leclerc

Publications and source records attributed to C Leclerc.

At least 181 records · Page 10Linked to original sources
PubMed1982

Demonstration of muramyl dipeptide (MDP)-induced T suppressor cells responsible for MDP immunosuppressive activity.

Muramyl dipeptide (MDP), a synthetic immunostimulant, has been previously shown to increase or decrease the humoral and cellular immune responses, depending upon the experimental conditions used. In the present study we have investigated the mechanisms of MDP-induced immunosuppression. After repeated injections of high dosages of MDP in vivo, both adherent and B cell-enriched cell populations from MDP-treated mice were able to collaborate with normal complementary populations. In contrast, T cell-enriched populations exhibited suppressive activity which could be removed by treatment with anti-Thy-1.2 antiserum and complement. These results clearly indicate that MDP-induced immunosuppression is mediated by T cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Visceral Leishmania tropica infection of BALB/c mice: cellular analysis of in vitro unresponsiveness to sheep erythrocytes.

In mice, infection with Leishmania tropica initially produced a nonspecific enhancement of the immune response to sheep erythrocytes as measured both in vitro and in vivo. Subsequently, the spleen cell responses of susceptible mice (BALB/c) to sheep erythrocytes and T- and B-cell mitogens in vitro decreased dramatically, whereas those of the resistant strain (C57BL/6) returned to normal. Analysis of the spleen cells of infected animals revealed that macrophages (the target cells of Leishmania) were not defective. However, both T- and B-cell-depleted splenocyte populations of infected animals lacked the ability to respond in the presence of their corresponding B- and T-cell-depleted populations of normal spleen cells. It was also observed that the addition of various numbers of Leishmania organisms did not alter the response of normal spleen cells in vitro. The results of cocultures of various ratios of cells from the spleen of infected and normal animals ruled out the possibility of a strong active immunosuppression. The decrease of in vitro response is attributed to the depletion of immunocompetent cells in the spleen of infected mice, which is heavily populated by null cells.

Animals↗
PubMed1981

Systemic infection of Leishmania tropica (major) in various strains of mice.

The spleen cells of different strains of mice were cultured and examined for the presence of viable promastigotes one to three months following a cutaneous inoculation of 1 to 2 X 10(6) promastigotes of Leishmania tropica (major). The spleen cultures of all five strains tested (BALB/c, DBA/3, C3H, CBA and C57B1/6) contained organisms. Viable parasites were present in the spleen of resistant strains (C3H, CBA, C57B1/6) even after recovery from their cutaneous lesion. The possible implication of this finding in the long lasting immunity observed in this disease is discussed.

Animals↗
PubMed1981

Studies on visceral Leishmania tropica infection in BALB/c mice. I. Clinical features and cellular changes.

The visceral and lethal infection produced in BALB/c mice by Leishmania tropica (major) is accompanied by splenomegaly, anaemia and reversal of albumin-to-globulin ratio. The percentages of both B and T cells are decreased in the spleen. The spleen and lymph nodes become populated with large Ig-, Thy 1.2- 'null' cells. The similarity of some of these parameters with those produced in human kala-azar is discussed.

Animals↗
PubMed1980

Induction of antibodies directed against self and altered-self determinants by a synthetic adjuvant, muramyl dipeptide and some of its derivatives.

In a serum free, 2-mercaptoethanol supplemented culture medium muramyl dipeptide (MDP) is able to increase the number of plaque-forming cells (PFC) directed against syngeneic, bromelain-treated red blood cells (br-MRBC) and against an autoantigen, mouse albumin. The non-specific stimulation of anti-br-MRBC PFC by MDP, as by bacterial lipopolysaccharide (LPS), can be observed in spleen cell populations depleted of adherent and phagocytic cells, and in nu/nu spleen cell cultures. However, the kinetics of the induction of anti-br-MRBC PFC in murine spleen cell cultures in presence of LPS or of MDP are not identical. Moreover, MDP is able to stimulate C3H/He Orl (LPS low-responder strain) cells. Thus, the mechanisms of non-specific stimulation by MDP or by LPS could be different. Experiments done with thirteen structural analogues of MDP showed that there exists a good correlation between the adjuvant activity and the ability to induce anti-br-MRBC PFC.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Inhibition of mitogen-induced polyclonal activation by by a synthetic adjuvant, muramyl dipeptide (MDP).

A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), was previously shown to enhance polyclonal antibody response in murine spleen cell cultures. When MDP was added to the culture together with a potent murine B cell mitogen (such as bacterial lipopolysaccharide (LPS)), it inhibited completely the LPS-induced polyclonal activation without affecting either the 3H-thymidine incorporation or the number of blast cells in cultures. Strong suppression of mitogen-induced polyclonal activation by MDP was obtained by using a large range of cell concentrations in cultures and over various dosage levels of the stimulating mitogens (LPS and NWSM). An inhibition could be obtained even when MDP was added 24 hr after the addition of the mitogen, and highly significant suppression was observed in the absence of cell division in the cultures.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Enhancement by muramyl dipeptide of in vitro nude mice responses to a T-dependent antigen.

N-acetyl-muramyl-L-alanyl-D-isoglutamine (referred to as MDP for muramyl dipeptide) has been shown to enhance in vivo and in vitro immune responses to various antigens. It has previously been reported that in the case of T-dependent antigens, the adjuvant activity of MDP was mediated by a helper T-cell. Our present findings demonstrate that in vitro responses of nude mice spleen cells to T-independent, TNP-PAA or T-dependent SRBC can also be markedly increased by this synthetic adjuvant. Moreover, under the same conditions, MDP produced polyclonal activation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

The macrophage, target cell of the synthetic adjuvant muramyl dipeptide.

The mechanism of adjuvant activity of the synthetic glycopeptide N-acetylmuramul-L-alanyl-D-isoglutamine or muramyl dipeptide (MDP) was studied using in vitro plaque-forming cell (PFC) response to sheep erythrocytes (SRBC). Addition of MDP to DBA/2 mouse spleen cell cultures resulted regularly in a 2 to 3-fold increase of PFC numbers/10(6) recovered cells (p less than 0.01). Supernates (SPN) from MDP-stimulated cultures added to standard spleen cell + SRBC cultures brought about even more important increases of PFC numbers (p less than 0.01 to p less than 0.001). SPN from cultures supplemented with MDP alone (without SRBC) were more active than those of cell + MDP + SRBC cultures, and SPN removed on day 3 of culture were more active than those of day 5. This activity of SPN was maintained accross an H-2 histocompatibility barrier. Although pretreatment of spleen cells with anti-theta antigen serum entirely suppressed the anti-SRBC PFC response in spite of the presence of MDP, SPN from these cultures were as active as SPN from normal spleen cell MDP-stimulated cultures. In contrast, pretreatment of spleen cells with specific rabbit anti-mouse macrophage serum entirely suppressed both anti-SRBC response and SPN activity. It was concluded that the target cell for MDP is the macrophage which releases factors ultimately acting on B cells through T cell mediation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

Influence of a synthetic adjuvant (MDP) on qualitative and quantitative changes of serum globulins.

Administered to guinea-pig, a synthetic compound, N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), has been previously shown to substitute for Mycobacteria in Freund's complete adjuvant. Moreover, MDP increases the humoral immune response even when administered in an aqueous solution to mice. In the present report, it was demonstrated that administered to guinea-pig in a water-in-oil emulsion, MDP or active analogues favoured the production of IgG2 antibodies against ovalbumin. In contrast, derivatives of MDP which had no adjuvant activity failed to induce this particular class of immunoglobulins. MDP without antigen, in contrast with LPS or FCA, did not induce changes in immunoglobulin levels in mice. Administered in mice with an antigen, MDP induces an increase of IgG1 although the immunoglobulin levels are lower than those observed after immunization with adjuvants injected in a water-in-oil emulsion.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

Role of major and minor histocompatibility antigens in the suppression of alloreactive cytotoxic responses induced by alloantigen pretreatment.

We have recently shown that priming mice with allogeneic strain A spleen cells before immunization with (A x B)F1 spleen cells strongly suppresses the cytotoxic T-lymphocyte (CTL) response directed against linked strain B alloantigens. This specific decrease in the CTL responses against the second immunizing alloantigen is associated with a high CTL response against the first priming alloantigen. The suppression of CTL responses against the strain B alloantigens is, however, not due to killing of F1 spleen cells by anti-A CTL, since it was observed after immunization of primed mice with a mixture of (A x B)F1 and B cells. In the present study, attempts were made to determine the relative contribution of H-2 and minor histocompatibility background antigens towards induction of suppression. Our results demonstrate that priming and immunizing spleen cells have only to share H-2 antigens in order to induce a downregulation of CTL responses directed against the linked alloantigens. This indicates that immunity against H-2 antigens is sufficient to induce suppression. However, priming against minor histocompatibility antigens also induces suppression, but only if spleen cells used for priming and immunization share H-2 antigens with the recipient strain. Therefore, the suppression can be induced by priming with non-H-2 antigens but is H-2-restricted. This study has also demonstrated that suppression can be induced by intraperitoneal or subcutaneous administration of allogeneic cells.

Animals↗