PubMed Health⌕ Search

Biomedical subjects

L Pelletier

Publications and source records attributed to L Pelletier.

At least 19 recordsLinked to original sources
PubMed1992

[Compliance with treatment in diabetic adolescents].

The study of compliance with therapy among teenagers with diabetes mellitus is a challenging task. Although several studies have addressed this problem, available knowledge in this field remains scant and the lack of understanding of factors which determine compliance with therapy hinders the development of interventions capable of helping diabetic teenagers to improve their quality of life. On the basis of a review of the relevant literature, this paper discusses compliance with therapy in the light of the specific features of teenage development. The two main theoretical models used to explain compliance with therapy in adolescent diabetics are presented. Parameters of compliance with therapy and the methods used to measure these parameters are also discussed.

Adolescent↗
PubMed1991

HgCl2-induced perturbation of the T cell network in experimental allergic encephalomyelitis. I. In vitro characterization of T cells involved.

Mercuric chloride (HgCl2) induces in Lewis (LEW) rats a non-antigen-specific immunosuppression and is able to down-modulate experimental allergic encephalomyelitis in about 70% of the rats. The aim of the present study was to determine the frequencies of lymph node cells involved in the proliferative response to myelin basic protein in rats injected with HgCl2 and immunized with myelin by using limiting dilution analysis (LDA). Highly frequent CD8+ T suppressor cells and at least 10-fold less frequent protein basic-specific T helper cells were detected in these rats. A third cell type allowing the proliferative response of Th cells in spite of Ts cells was also demonstrated. These cells, which could act as contrasuppressor cells, were CD4+ and adhered to Vicia villosa lectin; their frequency was in the same range as that of T helper cells. These data illustrate the potential role of different levels of T cell immunoregulatory activity in autoimmunity and the major interest of LDA in their analysis.

Animals↗
PubMed1991

HgCl2-induced perturbation of the T cell network in experimental allergic encephalomyelitis. II. In vivo demonstration of the role of T suppressor and contrasuppressor cells.

In the companion paper (J. Rossert et al., Cell. Immunol. 137, 1991), we showed by using limiting dilution analysis that Lewis (LEW) rats injected with HgCl2 and immunized with myelin (LEWHg/MYE) exhibit anti-basic protein CD4+ T helper cells (Th), at least 10-fold more frequent CD8+ T suppressor cells (Ts), and T contrasuppressor cells (Tcs). These Tcs cells were shown to be CD4+ T cells adhering to Vicia villosa (VV) lectin and allowed Th cells to proliferate despite the presence of Ts cells. The CD8+ Ts cells might be responsible for the protection from experimental allergic encephalomyelitis (EAE) observed in about 70% of LEW rats injected with HgCl2. The concomitant presence of CD4+ Tcs cells might explain that 30% of the rats escaped this protection. The aim of this work is to demonstrate in vivo the roles of CD8+ Ts cells and Tcs cells in mercury-induced protection from EAE. It will be shown that LEWHg/MYE rats depleted of CD8+ cells as well as LEWHg/MYE rats transferred with VV lectin-adherent Tcs cells develop EAE. These data demonstrate that CD8+ Ts cells are responsible for HgCl2-induced protection and that Tcs cells are involved in the control of Ts cells in vivo.

Animals↗
PubMed1991

[Manifestation of immunologic origin produced by toxic compounds].

Toxic agents may induce immunological manifestations by interfering with either non specific or specific pathways of immunity. The interference with the specific pathways may result in stimulatory (autoimmunity or hypersensitivity) or suppressive reactions. Mechanisms responsible for autoimmunity of hypersensitivity are now better understood. Hypersensitive reaction may be the consequence of the recognition by T cells of the xenobiotic presented by MHC class II molecules. Mechanisms leading to autoimmune reaction probably differ according to the nature of the drug. Thus drugs metabolized by liver enzymes could induce autoimmune hepatitis as a consequence of the binding of a reactive metabolite to the enzyme, thus rendered immunogenic. Other drugs like thiol or metal-containing chemicals could be responsible for autoimmunity reaction by interacting with molecules involved in T-B lymphocyte cooperation. The knowledge of the involved mechanisms should allow to develop predictive assays.

Allergens↗
PubMed1991

Effect of the thiol group on experimental gold-induced autoimmunity.

Brown Norway rats injected with aurothiopropanolsulfonate sodium salt develop systemic autoimmunity. The aim of this study was to assess the influence of the sulfur-containing group in this experimental model of gold-induced autoimmunity. It was shown that the sulfur-containing group does not induce autoimmunity of itself, but potentiates the immunotoxic effects of gold.

Animals↗
PubMed1991

Experimental gold-induced autoimmunity.

The pathogenesis of gold-induced autoimmunity and membranous glomerulopathy is not well understood. HgCl2 and D-penicillamine, other chemicals known to trigger membranous glomerulopathy in humans, induce autoimmune manifestations in Brown-Norway (BN) rats but not in Lewis (LEW) rats. These chemicals trigger T-cell clones which are specific for self class II molecules from the major histocompatibility complex and are probably responsible for the polyclonal B-cell activation observed. The aim of this work was to test the effects of aurothiopropanolsulphonate (ATPS) in BN and LEW rats. In BN rats, ATPS induced a polyclonal B-cell activation marked by lymphoproliferation, hyperimmunoglobulinaemia affecting mainly IgE, and by the production of numerous autoantibodies. A glomerulonephritis occurred, initially due to anti-glomerular basement membrane antibody deposition, and later to the formation of granular deposits, occasionally resulting in a typical membranous glomerulopathy. Self class-II-specific T-cells were found that might be responsible for the polyclonal B-cell activation. Lewis rats were free of glomerulopathy but, like BN rats, exhibited an interstitial nephritis and some degree of polyclonal B-cell activation. These findings demonstrate that, depending on the strain, ATPS triggers different B-cell clones inducing different degrees of autoimmunity.

Animals↗
PubMed1991

Thymic epithelial cell transplantation in patients with acquired immunodeficiency syndrome. Evidence for infection by HIV-I of newly differentiated T cells at the site of transplantation.

From October 1983 to July 1984, 11 adult AIDS patients have received single or repeated thymic grafts. All have had opportunistic infections and 3 also had Kaposi's sarcoma. Thymic tissue from infants undergoing cardiac surgery was cultured to provide a thymocyte- and fibroblast-free epithelial cell inoculum. 18-21 days post-explantation, cells and explants were injected intraperitoneally, intramuscularly or intrahepatically. Transplants were well tolerated in all cases. In 7 cases liver biopsy was performed at the time of grafting and 2 months later. Ten patients have died after a mean survival time following transplantation of 8.7 months while 1 patient was lost to follow up. Clinical improvement and absence of new opportunistic infections were apparent for 4 months following transplantation. Partial immunoreconstitution was evidenced by an increase in peripheral blood lymphocytes (8 of 10 cases) and lymphocyte subsets (7 of 10 cases) as well as by presence of T4 and T8 positive cells in the liver (5 of 7 cases). In 5 of 7 patients, double-staining immunofluorescence showed that HIV-I antigens were present in T4-phenotype cells, at the site of the graft, 2 months after grafting, but were not detected in the liver at the time of grafting. Transient immunoreconstitution, therefore, maybe related to destruction of newly differentiated T lymphocytes.

Acquired Immunodeficiency Syndrome↗
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↗