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Biomedical subjects

L Pelletier

Publications and source records attributed to L Pelletier.

At least 73 records · Page 4Linked to original sources
PubMed1990

D-penicillamine-induced autoimmunity in Brown-Norway rats. Similarities with HgCl2-induced autoimmunity.

D-penicillamine (DP) has been previously shown to induce an autoimmune disease in Brown-Norway (BN) rats, characterized by a dermatitis, by the production of antinuclear antibodies, by the formation fo circulating immune complexes, and by linear IgG deposits along the glomerular basement membrane. These manifestations are quite similar to those observed in mercuric chloride (HgCl2)-induced autoimmunity. The mechanism of the latter disease has been recently partly elucidated. The aim of this study was to compare DP and HgCl2-induced autoimmunity in BN rats and to compare the mechanisms involved in both situations. A transient increase in the number of spleen cells, affecting B cells and CD4+ T cells, and an increase in serum IgE concentration, previously reported in HgCl2-induced autoimmunity, were observed during DP treatment. Autoreactive anti-class II T cells able to proliferate not only in the presence of autologous B cells but also in the presence of syngeneic normal B cells were found in DP-treated BN rats. Spontaneous regulation occurred, associated with the disappearance of autoreactive T cells. Suppressor CD8+ T cells were not involved in this phenomenon. Mechanisms involved in both the induction and the regulation of DP-induced autoimmunity seem to be quite similar to those reported in HgCl2-induced autoimmunity.

Animals↗
PubMed1990

Rat anti-glomerular basement membrane antibodies in toxin-induced autoimmunity and in chronic graft-vs.-host reaction share recurrent idiotypes.

Cross-reactive idiotypes (CRId) borne on autoanti-glomerular basement membrane antibodies of Brown-Norway (BN) rats with mercury-induced glomerulonephritis have been described in the preceding study (Guéry, J.-C. et al., Eur. J. Immunol. 1990. 20:93). BN rats treated with sodium aurothiopropanol sulfonate or D-penicillamine, as well as (LEW X BN)F1 hybrids transferred with BN rat spleen cells, developed quite similar autoimmune abnormalities. In the present study, it is shown that immunoglobulins bearing such "public" idiotypes are also produced and deposited in the kidney in these three models. The CRId here described may, therefore, be considered as a marker of sets of recurrently expressed V region genes during the course of these autoimmune disorders. Anti-self class II T cells are present in the three models of toxin-induced autoimmunity and anti-allo class II T cells are responsible for the chronic graft-vs.-host reaction. The same B cell clones are probably triggered during these processes as a consequence of a polyclonal B cell activation mediated by anti-class II T cells.

Animals↗
PubMed1990

Graft-versus-host reactions in the rat mimic toxin-induced autoimmunity.

Gold salts, D-penicillamine or mercurials induce autoimmunity in Brown Norway (BN) rats and provoke an immunosuppression in Lewis (LEW) rats. It has been suggested that immunologically mediated manifestations induced by drugs could result from graft-versus-host (GVH) like reactions. We show that BN spleen cells transferred into (LEW x BN)F1 hybrids induce a chronic GVH reaction (GVHR). This reaction led to an autoimmune disease quite similar to that induced by drugs in BN rats. In both situations, a common part of the B cell repertoire is triggered. In contrast, LEW spleen cells transferred into (LEW x BN)F1 hybrids provoke a lethal GVHR. This is to be compared with the CD8-mediated immunosuppression observed in LEW rats injected with HgCl2. These findings are in agreement with the prediction that immune dysregulation induced by drugs leads to GVH-like reactions either stimulatory or suppressive depending upon the strain tested.

Animals↗
PubMed1990

Role of CD8+ T cells in mercury-induced autoimmunity or immunosuppression in the rat.

In Brown-Norway (BN) rats mercuric chloride induces an autoimmune disease characterized by an increase in serum IgE concentration, and by the production of anti-glomerular basement membrane antibodies responsible for a glomerulonephritis with a heavy proteinuria. (i) This disease results from a B-cell polyclonal activation probably due to frequent anti-class II T cells. (ii) The self limitation observed in this model is associated with both a decrease in the frequency of anti-class II T cells and the emergence of CD8+ T cells able to suppress these autoreactive T cells. (iii) In Lewis (LEW) rats which do not develop autoimmunity, HgCl2 provokes the appearance of non-antigen-specific CD8+ T cells responsible for a depression of T-cell functions. The aim of this work was to test the effect of treatment with an anti-CD8 monoclonal antibody (MoAb) in both BN and LEW rats. Anti-CD8 MoAb-treated rats were effectively depleted in CD8+ T cells. However, neither the induction nor regulation phases of mercury-induced autoimmunity were modified in BN rats. Mercury-induced immunosuppression in LEW rats was abrogated; however, depletion in CD8+ T cells did not allow the disease to occur in that strain. Finally, CD8 depletion induced in normal BN rats the appearance of rare anti-class II T cells showing that these cells are normally present in that strain but negatively controlled by suppressor T cells.

Animals↗
PubMed1990

[Health indicators and public health planning].

Health indicators are considered to be fundamental to the public health planning process. To a large extent, programs and services relevancy depends on indicators used for planning. Based upon a review of the literature, criteria for judging the acceptability of available indicators are presented and described. The principal health indicators developed for planning health programmes and services are then analysed in terms of these criteria. The dimensions of health measured by the various indicators are noted together with the relevancy and limits of each group of indicators analysed.

Activities of Daily Living↗
PubMed1989

[Immune glomerulopathies of toxic origin. Possible mechanisms of induction].

Mechanisms of toxic-induced autoimmunity including drug-induced autoimmune glomerulonephritis are unknown. In the mercury-induced autoimmune disease in Brown-Norway (BN) rats it has been shown that B cells are polyclonally activated provided that T cells are present. Autoreactive T cells that recognized self-Ia on normal B cells have been found to be highly frequent in HgCl2-injected BN rats. It has been possible to transfer all the autoimmune abnormalities by injecting T cells from HgCl2-exposed BN rats into normal syngeneic animals. However the recipient had to be depleted in suppressor/cytotoxic T cells by treatment with an anti-CD8 antibody for a full-blown disease to appear. These experiments show that a toxic agent may induce an autoimmune glomerulonephritis in the context of an autoimmune disease by generating or expanding anti-self Ia autoreactive T cells provided that suppressor/cytotoxic T cells have been inhibited. Autoreactive T cells are probably responsible for the polyclonal activation of B cells in this model. This mechanism does not rule out that other mechanisms could play a role.

Animals↗
PubMed1988

Autoreactive T cells in mercury-induced autoimmunity. Ability to induce the autoimmune disease.

It has been previously shown that autoreactive T cells appear during mercury-induced autoimmunity in Brown-Norway (BN) rats. In the present work, it is shown that: 1) T cells and T helper cells from HgCl2-injected BN rats are able to actively transfer autoimmunity in normal BN rats; the disease transferred is exacerbated when recipients are treated with the antisuppressor/cytotoxic T cell monoclonal antibody (OX8); 2) normal T cells preincubated with HgCl2 are also able to transfer the disease in OX8-treated but not in T cell-depleted rats; and 3) T cells from HgCl2-injected BN rats also transferred the disease in both normal and T cell depleted rats. It is concluded that: 1) autoreactive T cells, and presumably anti-Ia T cells are involved in the pathogenesis of mercury-induced autoimmunity; 2) these autoreactive T cells induce suppressor/cytotoxic T cells to proliferate in normal syngeneic recipients; the fact that this T cell subset did not proliferate in HgCl2-injected BN rats suggests that HgCl2 also affects T suppressor cells; and 3) mercury-induced autoimmunity could result from the additive effect of the emergence of autoreactive T cells and of a defect at the T suppressor level.

Animals↗
PubMed1988

Effect of HgCl2 on experimental allergic encephalomyelitis in Lewis rats. HgCl2-induced down-modulation of the disease.

HgCl2 induces autoimmunity in Brown-Norway rats and immunosuppression in Lewis rats. In the latter rats, HgCl2 triggers the proliferation of T suppressor/cytotoxic (OX8+) cells which actively suppress T cell functions. This led us to study the effect of HgCl2 on experimental allergic encephalomyelitis (EAE), a T cell-mediated autoimmune disease obtained following immunization with basic protein (BP). It will be shown that HgCl2 attenuates or even prevents clinical manifestations of EAE and inhibits both the proliferative response of T cells to BP and the anti-BP antibody response. This immunosuppression was not due to a defect at the T helper cell or antigen-processing cell level but to the emergence of T suppressor cells.

Animals↗
PubMed1988

Autoreactive T cells in mercury-induced autoimmunity. Demonstration by limiting dilution analysis.

Mercuric chloride is responsible in Brown-Norway rats for an autoimmune disease that is autoregulated. Previous studies have shown that this agent induces T cell-dependent polyclonal B cell activation in these rats. Evidence has also been obtained for the existence of autoreactive T cells which play a role in the evolution of this process. In the present study, limiting dilution analysis was used to demonstrate that (a) frequent autoreactive T helper cells which proliferate in the presence of T cells from HgCl2-injected rats are present from day 4; (b) frequent auto-anti-Ia T helper cells which recognize normal B cells as well as B cells from HgCl2-injected rats appear from day 6; and (c) less frequent T suppressor cells which could play a role in autoregulation emerge from day 14.

Animals↗
PubMed1988

[The needs in health considered within the perspective of an adolescent population.].

In the context of a program review in collaboration with a Community Health Department (DSC), the author examined how adolescents perceive their needs concerning health. Following a summary describing the methodology used to gather and analyse the data, the author looks at the main problems identified by teens and understood by them as a priority with regard to their health. Also discussed are solutions suggested by the adolescents, problems with parents and dependant behaviors. In conclusion, the author presents two clinical actions suggested by the study.

English Abstract↗
PubMed1988

HgC12 induces T and B cells to proliferate and differentiate in BN rats.

Mercuric chloride induces in Brown-Norway (BN) rats an autoimmune disease characterized by the production of various autoantibodies and by a marked increase in the IgE serum concentration. This agent is responsible for a T dependent polyclonal activation of B cells, which is probably due to the emergence of autoreactive T cells. The aim of this study was to evaluate the effect of HgCl2 injections on lymphoid organs and on the serum concentration of the various Ig isotypes. HgCl2 induced (1) a lymphoproliferation in spleen and lymph nodes involving B and T helper cells while the number of T suppressor/cytotoxic cells was not modified, (2) an increase in the number of Ig containing cells resulting in a rise in all serum Ig isotypes, and (3) an early thymic atrophy probably immunologically mediated, which was not involved in the induction phase of the disease since adult thymectomy had no effect. These findings demonstrate that the polyclonal effect of HgCl2 is not isotype-restricted although the IgE response is predominantly affected and they support evidence for a major role for an excess of T help in the HgCl2-induced polyclonal activation of B cells. It was also observed that B cell areas are present in normal BN rat thymuses, the potential role of which in the induction of autoimmunity remains to be investigated.

Animals↗
PubMed1988

Distinct phenotypic composition of diffuse interstitial and perivascular focal infiltrates in renal allografts: a morphometric analysis of cellular infiltration under conventional immunosuppressive therapy and under cyclosporine A.

Phenotypic analysis of interstitial mononuclear cell infiltrates was undertaken in 40 transplant renal specimens obtained from 38 patients in order to assess the influence of immunosuppressive therapy. Thirteen patients were given conventional immunosuppressive treatment (azathioprine and prednisone) and the other 25 received cyclosporine. The immunostaining was performed using seven antileucocyte antibodies by alkaline phosphatase-anti-alkaline phosphatase method. Interstitial infiltrates were distributed in two patterns: diffuse infiltrates and periglomerular/perivascular aggregates. The phenotypic composition was distinct in these two patterns: in diffuse infiltrates, monocytes/macrophages (EBM 11) represented the predominant inflammatory cell and were associated with a minor component of T cells (T 11). In contrast, aggregates had a major T lymphocyte phenotype in addition with few foci of B cells. T4 subset of T lymphocytes always predominated over T8 subset. The repartition and the proportion of each cell type were not significantly different in rejecting and not rejecting grafts and were not affected by the immunosuppressive regimen.

Administration, Oral↗
PubMed1987

HgCl2 induces nonspecific immunosuppression in Lewis rats.

Brown-Norway (BN) rats injected with HgCl2 have been previously shown to develop a variety of autoimmune abnormalities. The susceptibility of BN rats is genetically controlled, and Lewis rats bearing a different RT1 haplotype are resistant. It will be shown in the present study that the number of MRC OX-8+ (suppressor/cytotoxic) cells increases in the spleen and lymph nodes of Lewis rats injected with HgCl2. The responsiveness to T cell mitogens and to alloantigens is concomitantly inhibited. Spleen cells from Lewis rats injected with HgCl2 fail to induce a local graft-vs.-host reaction. Data presented show that MRC OX-8+ cells are involved in the immunosuppression in Lewis rats treated with HgCl2. Furthermore, lymph node cells and MRC OX-8+ cells from these rats are able to inhibit the normal mixed lymphocyte reaction indicating that suppression is active. Thus, HgCl2 is able to trigger immune dysregulation leading either to autoimmunity or to immunosuppression depending upon the genetic background of the rat strain tested.

Animals↗